J. N. George, Platelets. Lancet, vol.355, pp.1531-1540, 2000.

T. Gremmel, A. Frelinger, and A. Michelson, Platelet physiology, Semin Thromb Hemost, vol.42, pp.191-204, 2016.

J. N. Thon and J. E. Italiano, Platelets: production, morphology and ultrastructure, Antiplatelet agents. Berlin, Heidelberg, pp.3-22, 2012.

D. Zucker-franklin, Megakaryocyte and platelet structure in thrombocytopoiesis: the effect of cytokines, Stem Cells, vol.14, pp.1-17, 1996.

K. Kaushansky, Lineage-specific hematopoietic growth factors, N Engl J Med, vol.354, pp.2034-2079, 2006.

J. E. Italiano, P. Lecine, R. A. Shivdasani, and J. H. Hartwig, Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes, J Cell Biol, vol.147, pp.1299-312, 1999.

E. Lefrançais, G. Ortiz-muñoz, A. Caudrillier, B. Mallavia, F. Liu et al., The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors, Nature, vol.544, pp.105-114, 2017.

C. P. Mercado and F. Kilic, Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels, Mol Interv, vol.10, pp.231-272, 2010.

J. P. Mcredmond, Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes, Mol Cell Proteomics, vol.3, pp.133-177, 2003.

P. Landry, I. Plante, D. L. Ouellet, M. P. Perron, G. Rousseau et al., Existence of a microRNA pathway in anucleate platelets, Nat Struct Mol Biol, vol.16, pp.961-967, 2009.

H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nat Cell Biol, vol.9, pp.654-663, 2007.

K. Broos, H. B. Feys, D. Meyer, S. F. Vanhoorelbeke, K. Deckmyn et al., Platelets at work in primary hemostasis, Blood Rev, vol.25, pp.155-67, 2011.

J. Emsley, C. G. Knight, R. W. Farndale, M. J. Barnes, and R. C. Liddington, Structural basis of collagen recognition by integrin ?2?1, Cell, vol.101, pp.47-56, 2000.

K. Furihata, K. J. Clemetson, H. Deguchi, and T. J. Kunicki, Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity, Arterioscler Thromb Vasc Biol, vol.21, pp.1857-63, 2001.

J. G. White, M. D. Krumwiede, D. K. Johnson, and G. Escolar, Redistribution of GPIb/IX and GPIIb/IIIa during spreading of discoid platelets, Br J Haematol, vol.90, pp.633-677, 1995.

T. Xiao, J. Takagi, B. S. Coller, J. Wang, and T. A. Springer, Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics, Nature, vol.432, pp.59-67, 2004.

J. Jin, J. L. Daniel, and S. P. Kunapuli, Molecular basis for ADP-induced platelet activation II. The P2Y1 Receptor Mediates ADP-induced intracellular calcium mobilization and shape change in platelets, J Biol Chem, vol.273, pp.2030-2034, 1998.

M. L. Kahn, Y. Zheng, W. Huang, V. Bigornia, D. Zeng et al., A dual thrombin receptor system for platelet activation, Nature, vol.394, pp.690-694, 1998.

F. Gaertner, Z. Ahmad, G. Rosenberger, S. Fan, L. Nicolai et al., Migrating platelets are mechano-scavengers that collect and bundle Bacteria, Cell, vol.171, p.23, 2017.

B. Laffont, A. Corduan, H. Ple, A. Duchez, N. Cloutier et al., Activated platelets can deliver mRNA regulatory Ago2bulletmicroRNA complexes to endothelial cells via microparticles, Blood, vol.122, pp.253-61, 2013.

B. Laffont, A. Corduan, M. Rousseau, A. Duchez, C. Lee et al., Platelet microparticles reprogram macrophage gene expression and function, Thromb Haemost, vol.115, pp.311-334, 2016.

M. Baj-krzyworzeka, M. Majka, D. Pratico, J. Ratajczak, G. Vilaire et al., Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells, Exp Hematol, vol.30, pp.450-459, 2002.

O. P. Barry, D. Pratico, J. A. Lawson, and G. A. Fitzgerald, Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles, J Clin Invest, vol.99, pp.2118-2145, 1997.

N. Arraud, R. Linares, S. Tan, C. Gounou, J. Pasquet et al., Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration, J Thromb Haemost, vol.12, pp.614-641, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00996592

J. Pereira, G. Alfaro, M. Goycoolea, T. Quiroga, M. Ocqueteau et al., Circulating platelet-derived microparticles in systemic lupus erythematosus. Association with increased thrombin generation and procoagulant state, Thromb Haemost, vol.95, pp.94-103, 2005.

I. Melki, N. Tessandier, A. Zufferey, and E. Boilard, Platelet microvesicles in health and disease, Platelets, vol.2017, pp.1-8

N. Key and N. Mackman, Tissue factor and its measurement in whole blood, plasma, and microparticles, Semin Thromb Hemost, vol.36, pp.865-75, 2010.

P. J. Sims, T. Wiedmer, C. T. Esmon, H. J. Weiss, and S. J. Shattil, Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity, J Biol Chem, vol.264, pp.17049-57, 1989.

F. Gaertner and S. Massberg, Blood coagulation in immunothrombosis-at the frontline of intravascular immunity, Semin Immunol, vol.28, pp.561-570, 2016.

M. Koupenova, O. Vitseva, C. R. Mackay, L. M. Beaulieu, E. J. Benjamin et al., Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis, Blood, vol.124, pp.791-802, 2014.

D. Turpin, M. Truchetet, B. Faustin, A. Contin-bordes, C. Brisson et al., Role of extracellular vesicles in autoimmune diseases, Autoimmun Rev, vol.15, pp.174-83, 2016.

J. E. Joseph, P. Harrison, I. J. Mackie, D. A. Isenberg, and S. J. Machin, Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis, Br J Haematol, vol.115, pp.451-460, 2001.

S. Nhek, R. Clancy, K. A. Lee, N. M. Allen, T. J. Barrett et al., Activated platelets induce endothelial cell activation via an Interleukin-1? pathway in systemic lupus erythematosus, Arterioscler Thromb Vasc Biol, 2017.

M. B. Kahaleh, I. Osborn, and E. C. Leroy, Elevated levels of circulating platelet aggregates and beta-thromboglobulin in scleroderma, Ann Intern Med, vol.96, pp.610-613, 1982.

M. J. Goodfield, M. A. Orchard, and N. R. Rowell, Whole blood platelet aggregation and coagulation factors in patients with systemic sclerosis, Br J Haematol, vol.84, pp.675-80, 1993.

M. C. Hochberg, Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum, vol.40, p.1725, 1997.

M. Petri, A. Orbai, G. S. Alarcón, C. Gordon, J. T. Merrill et al., Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus, Arthritis Rheum, vol.64, pp.2677-86, 2012.

A. Galil, S. M. Edrees, A. M. Ajeeb, A. K. Aldoobi, G. S. El-boshy et al., Prognostic significance of platelet count in SLE patients, Platelets, vol.28, pp.203-210, 2017.

P. D. Ziakas, Lupus thrombocytopenia: clinical implications and prognostic significance, Ann Rheum Dis, vol.64, issue.9, p.1366, 2005.

C. C. Mok, A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population, Rheumatology, vol.39, pp.399-406, 2000.

J. C. Nossent and A. J. Swaak, Prevalence and significance of haematological abnormalities in patients with systemic lupus erythematosus, Q J Med, vol.80, pp.605-617, 1991.

R. A. Frayha, L. E. Shulman, and M. B. Stevens, Hematological abnormalities in scleroderma, Acta Haematol, vol.64, pp.25-30, 1980.

L. Czirják, I. Molnár, I. Csipö, M. Szabolcs, A. Mihály et al., Anti-platelet antibodies against gpIIb/IIIa in systemic sclerosis, Clin Exp Rheumatol, vol.12, pp.527-536, 1994.

Z. Li, M. K. Delaney, K. A. O'brien, and X. Du, Signaling during platelet adhesion and activation, Arterioscler Thromb Vasc Biol, vol.30, pp.2341-2350, 2010.

G. Escolar, M. Krumwiede, and J. G. White, Organization of the actin cytoskeleton of resting and activated platelets in suspension, Am J Pathol, vol.123, pp.86-94, 1986.

S. Yavuz and A. Ece, Mean platelet volume as an indicator of disease activity in juvenile SLE, Clin Rheumatol, vol.33, pp.637-678, 2014.

M. Bai, L. Xing, J. Feng, C. Cui, L. Huang et al., Mean platelet volume could reflect disease activity of adult patients with systemic lupus erythematosus, Clin Lab, vol.62, 2016.

C. Lood, H. Tydén, B. Gullstrand, C. T. Nielsen, N. Heegaard et al., Decreased platelet size is associated with platelet activation and anti-phospholipid syndrome in systemic lupus erythematosus, Rheumatology, vol.56, issue.3, pp.408-424, 2017.

S. Soydinc, I. H. Turkbeyler, Y. Pehlivan, G. Soylu, M. F. Goktepe et al., Mean platelet volume seems to be a valuable marker in patients with systemic sclerosis, Inflammation, vol.37, pp.100-106, 2014.

P. Noris, F. Melazzini, and C. L. Balduini, New roles for mean platelet volume measurement in the clinical practice?, Platelets, vol.27, pp.607-619, 2016.

A. H. Charafeddine, E. J. Kim, D. M. Maynard, H. Yi, T. A. Weaver et al., Platelet-derived CD154: ultrastructural localization and clinical correlation in organ transplantation, Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg, vol.12, pp.3143-51, 2012.

J. Viallard, A. Solanilla, B. Gauthier, C. Contin, J. Déchanet et al., Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis, Blood, vol.99, pp.2612-2616, 2002.
URL : https://hal.archives-ouvertes.fr/inserm-02519484

P. Duffau, J. Seneschal, C. Nicco, C. Richez, L. E. Douchet et al., Platelet CD154 potentiates interferon-secretion by plasmacytoid dendritic cells in systemic lupus erythematosus, Sci Transl Med, vol.2, pp.47-63, 2010.

M. Nagahama, S. Nomura, Y. Ozaki, C. Yoshimura, H. Kagawa et al., Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus, Autoimmunity, vol.33, pp.85-94, 2001.

G. E. Pamuk, B. Turgut, Ö. N. Pamuk, Ö. Vural, M. Demir et al., Increased circulating platelet-leucocyte complexes in patients with primary Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis: a comparative study, Blood Coagul Fibrinolysis, vol.18, pp.297-302, 2007.

K. Komura, M. Fujimoto, T. Matsushita, K. Yanaba, M. Kodera et al., Increased serum soluble CD40 levels in patients with systemic sclerosis, J Rheumatol, vol.34, pp.353-361, 2007.

A. A. Ponomareva, T. A. Nevzorova, E. R. Mordakhanova, I. A. Andrianova, L. Rauova et al., Intracellular origin and ultrastructure of platelet-derived microparticles, J Thromb Haemost, vol.15, pp.1655-67, 2017.

T. Yahata, C. Suzuki, A. Yoshioka, A. Hamaoka, and K. Ikeda, Platelet activation dynamics evaluated using platelet-derived microparticles in Kawasaki disease, Circ J Off J Jpn Circ Soc, vol.78, pp.188-93, 2014.

Y. Chen, Y. Xiao, Z. Lin, X. X. He, C. Bihl et al., The role of circulating platelets microparticles and platelet parameters in acute ischemic stroke patients, J Stroke Cerebrovasc Dis, vol.24, pp.2313-2333, 2015.

P. López, J. Rodríguez-carrio, A. Martínez-zapico, L. Caminal-montero, and A. Suárez, Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity, Int J Cardiol, vol.236, pp.138-182, 2017.

P. R. Fortin, N. Cloutier, V. Bissonnette, E. Aghdassi, L. Eder et al., Distinct subtypes of microparticle-containing immune complexes are associated with disease activity, damage, and carotid intima-media thickness in systemic lupus erythematosus, J Rheumatol, vol.43, pp.2019-2044, 2016.

E. M. Mccarthy, D. Moreno-martinez, F. L. Wilkinson, N. J. Mchugh, I. N. Bruce et al., Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease, BBA Clin, vol.7, pp.16-22, 2017.

G. C. Tsokos, M. S. Lo, P. C. Reis, and K. E. Sullivan, New insights into the immunopathogenesis of systemic lupus erythematosus, Nat Rev Rheumatol, vol.12, pp.716-746, 2016.

D. Kim, A. Peck, D. Santer, P. Patole, S. M. Schwartz et al., Induction of interferon-? by scleroderma sera containing autoantibodies to topoisomerase I: association of higher interferon-? activity with lung fibrosis, Arthritis Rheum, vol.58, pp.2163-73, 2008.

P. Blanco, H. Ueno, and N. Schmitt, T follicular helper (Tfh) cells in lupus: activation and involvement in SLE pathogenesis: highlights, Eur J Immunol, vol.46, pp.281-90, 2016.

H. Zhi, J. Dai, J. Liu, J. Zhu, D. K. Newman et al., Platelet activation and Thrombus formation over IgG immune complexes requires integrin ?IIb?3 and Lyn kinase, PLoS One, vol.10, 2015.

M. D. Berlacher, J. A. Vieth, B. C. Heflin, S. R. Gay, A. J. Antczak et al., Fc?RIIa ligation induces platelet hypersensitivity to thrombotic stimuli, Am J Pathol, vol.182, pp.244-54, 2013.

C. T. Nielsen, O. Østergaard, L. Stener, L. V. Iversen, L. Truedsson et al., Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation, Arthritis Rheum, vol.64, pp.1227-1263, 2012.

F. Cognasse, The inflammatory role of platelets via their TLRs and Siglec receptors, Front Immunol, vol.6, 2015.

B. D. Poole, R. H. Scofield, J. B. Harley, and J. A. James, Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus, Autoimmunity, vol.39, pp.63-70, 2006.

G. Moroncini, S. Mori, C. Tonnini, and A. Gabrielli, Role of viral infections in the etiopathogenesis of systemic sclerosis, Clin Exp Rheumatol, vol.31, pp.3-7, 2013.

P. E. Love, Antiphospholipid antibodies: Anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders: prevalence and clinical significance, Ann Intern Med, vol.112, p.682, 1990.

N. Assous, Y. Allanore, F. Batteux, C. Meune, P. Toulon et al., Prevalence of antiphospholipid antibodies in systemic sclerosis and association with primitive pulmonary arterial hypertension and endothelial injury, Clin Exp Rheumatol, vol.23, pp.199-204, 2005.

K. B. Morrisroe, W. Stevens, H. Nandurkar, D. Prior, V. Thakkar et al., The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis, Clin Exp Rheumatol, vol.32, pp.133-137, 2014.

W. Zhang, F. Gao, D. Lu, N. Sun, X. Yin et al., Anti-?2 glycoprotein I antibodies in complex with ?2 glycoprotein I induce platelet activation via two receptors: apolipoprotein E receptor 2? and glycoprotein I b?, Front Med, vol.10, pp.76-84, 2016.

M. A. Khamashta, E. N. Harris, A. E. Gharavi, G. Derue, A. Gil et al., Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes, Ann Rheum Dis, vol.47, pp.849-54, 1988.

C. Lood, H. Tydén, B. Gullstrand, G. Sturfelt, A. Jönsen et al., Platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus, PLoS One, vol.9, p.99386, 2014.

T. M. Chiang, A. Rinaldy, and A. H. Kang, Cloning, characterization, and functional studies of a nonintegrin platelet receptor for type I collagen, J Clin Invest, vol.100, pp.514-535, 1997.

T. M. Chiang, H. Takayama, and A. E. Postlethwaite, Increase in platelet non-integrin type I collagen receptor in patients with systemic sclerosis, Thromb Res, vol.117, pp.299-306, 2006.

R. Cervera, M. A. Khamashta, J. Font, G. D. Sebastiani, A. Gil et al., Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on systemic lupus erythematosus, Medicine (Baltimore), vol.72, pp.113-137, 1993.

F. E. Heimovski, J. A. Simioni, and T. L. Skare, Systemic lupus erythematosus and Raynaud's phenomenon, An Bras Dermatol, vol.90, pp.837-877, 2015.

A. Shemirani, B. Nagy, A. Takáts, K. Zsóri, C. András et al., Increased mean platelet volume in primary Raynaud's phenomenon, Platelets, vol.23, pp.312-318, 2012.

A. D. Widgerow, Ischemia-reperfusion injury: influencing the microcirculatory and cellular environment, Ann Plast Surg, vol.72, pp.253-60, 2014.

M. Jansen, D. Emal, G. Teske, M. C. Dessing, S. Florquin et al., Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps, Kidney Int, vol.91, pp.352-64, 2017.

V. Brinkmann, U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann et al., Neutrophil extracellular traps kill bacteria, Science, vol.303, pp.1532-1537, 2004.

S. R. Clark, A. C. Ma, S. A. Tavener, B. Mcdonald, Z. Goodarzi et al., Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood, Nat Med, vol.13, pp.463-472, 2007.

A. S. Kimball, A. T. Obi, J. A. Diaz, and P. K. Henke, The emerging role of NETs in venous thrombosis and immunothrombosis, Front Immunol, vol.7, 2016.

J. Dieker, J. Tel, E. Pieterse, A. Thielen, N. Rother et al., Circulating apoptotic microparticles in systemic lupus erythematosus patients drive the activation of dendritic cell subsets and prime neutrophils for NETosis: proinflammatory effects of circulating microparticles in SLE, Arthritis Rheum, vol.68, pp.462-72, 2016.

J. Berthelot, L. Goff, B. Neel, A. Maugars, Y. Hamidou et al., NETosis: at the crossroads of rheumatoid arthritis, lupus, and vasculitis, Joint Bone Spine, vol.84, pp.255-62, 2017.

G. Guggino, M. Lo-pizzo, D. Liberto, D. Rizzo, A. Cipriani et al., Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients: IL-9 pathway in systemic sclerosis, Clin Exp Immunol, vol.190, pp.208-224, 2017.

R. Lande, D. Ganguly, V. Facchinetti, L. Frasca, C. Conrad et al., Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus, Sci Transl Med, vol.3, pp.73-92, 2011.

D. Lindau, J. Mussard, A. Rabsteyn, M. Ribon, I. Kötter et al., TLR9 independent interferon ? production by neutrophils on NETosis in response to circulating chromatin, a key lupus autoantigen, Ann Rheum Dis, vol.73, pp.2199-207, 2014.

L. H. Boudreau, A. Duchez, N. Cloutier, D. Soulet, N. Martin et al., Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation, Blood, vol.124, pp.2173-83, 2014.

Q. Zhang, M. Raoof, Y. Chen, Y. Sumi, T. Sursal et al., Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature, vol.464, pp.104-111, 2010.

M. J. White, K. Mcarthur, D. Metcalf, R. M. Lane, J. C. Cambier et al., Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production, Cell, vol.159, pp.1549-62, 2014.

S. Caielli, S. Athale, B. Domic, E. Murat, M. Chandra et al., Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus, J Exp Med, vol.213, pp.697-713, 2016.

J. Etulain, K. Martinod, S. L. Wong, S. M. Cifuni, M. Schattner et al., P-selectin promotes neutrophil extracellular trap formation in mice, Blood, vol.126, pp.242-248, 2015.

A. Carestia, T. Kaufman, L. Rivadeneyra, V. I. Landoni, R. G. Pozner et al., Mediators and molecular pathways involved in the regulation of neutrophil extracellular trap formation mediated by activated platelets, J Leukoc Biol, vol.99, pp.153-62, 2016.

C. Arpin, J. Dechanet, C. Van-kooten, P. Merville, G. Grouard et al., Generation of memory B cells and plasma cells in vitro, Science, vol.268, pp.720-722, 1995.
URL : https://hal.archives-ouvertes.fr/hal-02474293

A. J. Miga, S. R. Masters, B. G. Durell, M. Gonzalez, M. K. Jenkins et al., Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions, Eur J Immunol, vol.31, pp.959-65, 2001.

Y. Allanore, D. Borderie, C. Meune, H. Lemarechal, S. Weber et al., Increased plasma soluble CD40 ligand concentrations in systemic sclerosis and association with pulmonary arterial hypertension and digital ulcers, Ann Rheum Dis, vol.64, pp.481-484, 2005.

J. Viallard, A. Solanilla, B. Gauthier, C. Contin, J. Déchanet et al., Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis, Blood, vol.99, pp.2612-2616, 2002.
URL : https://hal.archives-ouvertes.fr/inserm-02519484

B. D. Elzey, J. Tian, R. J. Jensen, A. K. Swanson, J. R. Lees et al., Platelet-mediated modulation of adaptive immunity: a communication link between innate and adaptive immune compartments, Immunity, vol.19, pp.9-19, 2003.

B. Maître, P. H. Mangin, A. Eckly, V. Heim, J. Cazenave et al., Immature myeloid dendritic cells capture and remove activated platelets from preformed aggregates, J Thromb Haemost, vol.8, pp.2262-72, 2010.

A. Solanilla, Platelet-associated CD154 in immune thrombocytopenic purpura, Blood, vol.105, pp.215-223, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00019938

V. Sisirak, B. Sally, D. 'agati, V. Martinez-ortiz, W. Özçakar et al., Digestion of chromatin in apoptotic cell microparticles prevents autoimmunity, Cell, vol.166, pp.88-101, 2016.

C. Lood, H. Tydén, B. Gullstrand, A. Jönsen, E. Källberg et al., Platelet-derived S100A8/A9 and cardiovascular disease in systemic lupus erythematosus: platelet S100A8/A9 and CVD in SLE, Arthritis Rheum, vol.68, pp.1970-80, 2016.

L. Van-bon, M. Cossu, A. Loof, F. Gohar, H. Wittkowski et al., Proteomic analysis of plasma identifies the toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype, Ann Rheum Dis, vol.73, pp.1585-1594, 2014.

R. Hesselstrand, M. Wildt, G. Bozovic, A. Andersson-sjöland, K. Andréasson et al., Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis, Respir Med, vol.107, pp.1079-86, 2013.

M. Van-zoelen, H. Yang, S. Florquin, J. Meijers, S. Akira et al., Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo, Shock Augusta Ga, vol.31, pp.280-284, 2009.

X. Li, Y. Yue, Y. Zhu, S. Xiong, and . Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis, Mol Immunol, vol.65, pp.177-88, 2015.

A. Duchez, L. H. Boudreau, G. S. Naika, J. Bollinger, C. Belleannée et al., Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A2-IIA, Proc Natl Acad Sci, vol.112, pp.3564-3567, 2015.

C. Lood, H. Tydén, B. Gullstrand, C. Klint, C. Wenglén et al., Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus, PLoS One, vol.10, p.125109, 2015.

C. Dees, A. Akhmetshina, P. Zerr, N. Reich, K. Palumbo et al., Platelet-derived serotonin links vascular disease and tissue fibrosis, J Exp Med, vol.208, pp.961-72, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00589662

M. Leon-ponte, G. P. Ahern, O. Connell, and P. J. , Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor, Blood, vol.109, pp.3139-3185, 2007.

Y. Chabbi-achengli, T. Coman, C. Collet, J. Callebert, M. Corcelli et al., Serotonin is involved in autoimmune arthritis through Th17 immunity and bone resorption, Am J Pathol, vol.186, pp.927-964, 2016.

N. Li, J. Ghia, H. Wang, J. Mcclemens, F. Cote et al., Serotonin activates dendritic cell function in the context of gut inflammation, Am J Pathol, vol.178, pp.662-71, 2011.

M. Scherlinger, Autoimmunity Reviews, vol.17, pp.625-635, 2018.

B. Zöller, X. Li, J. Sundquist, and K. Sundquist, Risk of subsequent coronary heart disease in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden, PLoS One, vol.7, p.33442, 2012.

S. R. Schoenfeld, S. Kasturi, and K. H. Costenbader, The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review, Semin Arthritis Rheum, vol.43, pp.77-95, 2013.

M. Hermansen, J. Lindhardsen, C. Torp-pedersen, M. Faurschou, and S. Jacobsen, The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study, Rheumatology (Oxford), vol.56, pp.709-724, 2017.

J. Nossent, N. Cikes, E. Kiss, A. Marchesoni, V. Nassonova et al., Current causes of death in systemic lupus erythematosus in Europe, Lupus, vol.16, pp.309-326, 2000.

M. Elhai, C. Meune, J. Avouac, A. Kahan, and Y. Allanore, Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies, Rheumatology (Oxford), vol.51, pp.1017-1043, 2012.

G. Ozen, N. Inanc, A. U. Unal, F. Korkmaz, M. Sunbul et al., Subclinical atherosclerosis in systemic sclerosis: not less frequent than rheumatoid arthritis and not detected with cardiovascular risk indices, Arthritis Care Res, vol.68, pp.1538-1584, 2016.

M. G. Tektonidou, E. Kravvariti, G. Konstantonis, N. Tentolouris, P. P. Sfikakis et al., Subclinical atherosclerosis in systemic lupus erythematosus: comparable risk with diabetes mellitus and rheumatoid arthritis, Autoimmun Rev, vol.16, pp.308-320, 2017.

C. Lood, S. Amisten, B. Gullstrand, A. Jonsen, M. Allhorn et al., Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease, Blood, vol.116, pp.1951-1958, 2010.

S. R. Schoenfeld, H. K. Choi, E. C. Sayre, and J. A. Aviña-zubieta, Risk of pulmonary embolism and deep venous thrombosis in systemic sclerosis: a general population-based study, Arthritis Care Res, vol.68, pp.246-53, 2016.

G. A. Ramirez, S. Franchini, P. Rovere-querini, M. G. Sabbadini, A. A. Manfredi et al., The role of platelets in the pathogenesis of systemic sclerosis, Front Immunol, vol.3, p.160, 2012.

D. Siegel-axel and M. Gawaz, Platelets and endothelial cells, Semin Thromb Hemost, vol.33, pp.128-163, 2007.

L. Van-bon, A. J. Affandi, J. Broen, R. B. Christmann, R. J. Marijnissen et al., Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis, N Engl J Med, vol.370, pp.433-476, 2014.

P. M. Ridker, B. M. Everett, T. Thuren, J. G. Macfadyen, W. H. Chang et al., Antiinflammatory therapy with Canakinumab for atherosclerotic disease, N Engl J Med, vol.377, pp.1119-1150, 2017.

P. M. Ridker, J. G. Macfadyen, B. M. Everett, P. Libby, T. Thuren et al., Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial, Lancet, vol.391, pp.319-347, 2017.

H. Wang, K. Kleiman, J. Wang, W. Luo, C. Guo et al., Deficiency of P-selectin glycoprotein ligand-1 is protective against the prothrombotic effects of interleukin-1?, J Thromb Haemost, vol.13, pp.2273-2279, 2015.

W. Luo, H. Wang, M. K. Ohman, C. Guo, K. Shi et al., P-selectin glycoprotein ligand-1 deficiency leads to cytokine resistance and protection against atherosclerosis in apolipoprotein E deficient mice, Atherosclerosis, vol.220, pp.110-117, 2012.

C. Scambi, S. Ugolini, T. S. Jokiranta, D. Franceschi, L. Bortolami et al., The local complement activation on vascular bed of patients with systemic sclerosis: a hypothesis-generating study, PLoS One, vol.10, p.114856, 2015.

J. Leffler, A. A. Bengtsson, and A. M. Blom, The complement system in systemic lupus erythematosus: an update, Ann Rheum Dis, vol.73, pp.1601-1607, 2014.

A. H. Kao, C. A. Mcburney, A. Sattar, A. Lertratanakul, N. L. Wilson et al., Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus, Transl Stroke Res, vol.5, pp.510-518, 2014.

C. Lood, S. Eriksson, B. Gullstrand, A. Jönsen, G. Sturfelt et al., Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus -a possible link to venous thrombosis?, Lupus, vol.21, pp.1423-1455, 2012.

O. A. Hamad, K. N. Ekdahl, P. H. Nilsson, J. Andersson, P. Magotti et al., Complement activation triggered by chondroitin sulfate released by thrombin receptoractivated platelets, J Thromb Haemost, vol.6, pp.1413-1434, 2008.

G. Saggu, C. Cortes, H. N. Emch, G. Ramirez, R. G. Worth et al., Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O), J Immunol, vol.190, pp.6457-67, 2013.

H. Kerr and A. Richards, Complement-mediated injury and protection of endothelium: lessons from atypical haemolytic uraemic syndrome, Immunobiology, vol.217, pp.195-203, 2012.

K. K. Hamilton, R. Hattori, C. T. Esmon, and P. J. Sims, Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex, J Biol Chem, vol.265, pp.3809-3823, 1990.

S. Saadi, R. A. Holzknecht, C. P. Patte, D. M. Stern, and J. L. Platt, Complement-mediated regulation of tissue factor activity in endothelium, J Exp Med, vol.182, pp.1807-1821, 1995.

P. J. Sims and T. Wiedmer, Induction of cellular procoagulant activity by the membrane attack complex of complement, Semin Cell Biol, vol.6, pp.275-82, 1995.

K. S. Kilgore, J. P. Shen, B. F. Miller, P. A. Ward, and J. S. Warren, Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM-1, J Immunol, vol.155, pp.1434-1475, 1995.

C. Schulz, A. Schäfer, M. Stolla, S. Kerstan, M. Lorenz et al., Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood: a critical role for P-selectin expressed on activated platelets, Circulation, vol.116, pp.764-73, 2007.

N. Gerdes, T. Seijkens, D. Lievens, M. Kuijpers, H. Winkels et al., Platelet CD40 exacerbates atherosclerosis by transcellular activation of endothelial cells and leukocytes, Arterioscler Thromb Vasc Biol, vol.36, pp.482-90, 2016.

E. Rainger, G. Chimen, M. Harrison, M. J. Yates, C. M. Harrison et al., The role of platelets in the recruitment of leukocytes during vascular disease, Platelets, vol.26, pp.507-527, 2015.

N. Maugeri, S. Franchini, L. Campana, M. Baldini, G. A. Ramirez et al., Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis, Autoimmunity, vol.45, pp.584-591, 2012.

K. Hayakawa, L. Pham, Z. S. Katusic, K. Arai, and E. H. Lo, Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery, Proc Natl Acad Sci U S A, vol.109, pp.7505-7515, 2012.

S. Y. Park, S. W. Lee, H. Y. Kim, W. S. Lee, K. W. Hong et al., HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1? activation, Eur J Immunol, vol.45, pp.1216-1243, 2015.

Y. Hirata, H. Kurobe, M. Higashida, D. Fukuda, M. Shimabukuro et al., HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9, Atherosclerosis, vol.231, pp.227-260, 2013.

M. Schiraldi, A. Raucci, L. M. Muñoz, E. Livoti, B. Celona et al., HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4, J Exp Med, vol.209, pp.551-63, 2012.

W. Sun, Y. Jiao, B. Cui, X. Gao, Y. Xia et al., Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis, Lab Investig J Tech Methods Pathol, vol.93, pp.626-664, 2013.

A. Yoshizaki, K. Komura, Y. Iwata, F. Ogawa, T. Hara et al., Clinical significance of serum HMGB-1 and sRAGE levels in systemic sclerosis: association with disease severity, J Clin Immunol, vol.29, pp.180-189, 2009.

X. Xu, W. Wu, W. Tu, H. Chu, X. Zhu et al., Increased expression of S100A8 and S100A9 in patients with diffuse cutaneous systemic sclerosis. A correlation with organ involvement and immunological abnormalities, Clin Rheumatol, vol.32, issue.10, p.1501, 2013.

L. Wang, H. Luo, X. Chen, Y. Jiang, and Q. Huang, Functional characterization of S100A8 and S100A9 in altering monolayer permeability of human umbilical endothelial cells, PLoS One, vol.9, p.90472, 2014.

G. Srikrishna, K. Panneerselvam, V. Westphal, V. Abraham, A. Varki et al., Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells, J Immunol, vol.166, pp.4678-88, 2001.

M. A. Sparks, N. A. Makhanova, R. C. Griffiths, J. N. Snouwaert, B. H. Koller et al., Thromboxane receptors in smooth muscle promote hypertension, vascular remodeling, and sudden death, J Hypertens, vol.61, pp.166-73, 2013.

M. Félétou, R. Köhler, and P. M. Vanhoutte, Endothelium-derived vasoactive factors and hypertension: possible roles in pathogenesis and as treatment targets, Curr Hypertens Rep, vol.12, pp.267-75, 2010.

I. A. Reilly, L. Roy, and G. A. Fitzgerald, Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud's phenomenon, Br Med J (Clin Res Ed), vol.292, pp.1037-1046, 1986.

R. M. Tuder, C. D. Cool, M. W. Geraci, J. Wang, S. H. Abman et al., Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension, Am J Respir Crit Care Med, vol.159, pp.1925-1957, 1999.

P. R. Lev, J. P. Salim, R. F. Marta, M. Osorio, N. P. Goette et al., Platelets possess functional TGF-beta receptors and Smad2 protein, Platelets, vol.18, pp.35-42, 2007.

A. Meyer, W. Wang, J. Qu, L. Croft, J. L. Degen et al., Platelet TGF-?1 contributions to plasma TGF-?1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload, Blood, vol.119, pp.1064-74, 2012.

R. B. Christmann, P. Sampaio-barros, G. Stifano, C. L. Borges, C. R. De-carvalho et al., Association of Interferon-and transforming growth factor ?-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis, Arthritis Rheumatol, vol.66, pp.714-739, 2014.

R. Lafyatis, Transforming growth factor ?-at the centre of systemic sclerosis, Nat Rev Rheumatol, vol.10, pp.706-725, 2014.

F. Verrecchia and A. Mauviel, Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation, J Invest Dermatol, vol.118, pp.211-216, 2002.

F. Verrecchia, A. Mauviel, and D. Farge, Transforming growth factor-? signaling through the Smad proteins: role in systemic sclerosis, Autoimmun Rev, vol.5, pp.563-572, 2006.
URL : https://hal.archives-ouvertes.fr/inserm-00166114

E. Y. Kissin, R. Lemaire, J. H. Korn, and R. Lafyatis, Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation, Arthritis Rheum, vol.46, pp.3000-3009, 2002.

C. Solé, M. Gimenez-barcons, B. Ferrer, J. Ordi-ros, and J. Cortés-hernández, Microarray study reveals a transforming growth factor-?-dependent mechanism of fibrosis in discoid lupus erythematosus, Br J Dermatol, vol.175, pp.302-315, 2016.

J. R. Seibold and J. N. Harris, Plasma beta-thromboglobulin in the differential diagnosis of Raynaud's phenomenon, J Rheumatol, vol.12, pp.99-103, 1985.

K. L. Kaplan and J. Owen, Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo, Blood, vol.57, pp.199-202, 1981.

O. Kowal-bielecka, K. Kowal, A. Lewszuk, A. Bodzenta-lukaszyk, J. Walecki et al., Beta thromboglobulin and platelet factor 4 in bronchoalveolar lavage fluid of patients with systemic sclerosis, Ann Rheum Dis, vol.64, pp.484-490, 2005.

M. M. Zaldivar, K. Pauels, P. Von-hundelshausen, M. Berres, P. Schmitz et al., CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis, J Hepatol, vol.51, pp.1345-53, 2010.

A. Usategui, G. Criado, E. Izquierdo, D. Rey, M. J. Carreira et al., A profibrotic role for thymic stromal lymphopoietin in systemic sclerosis, Ann Rheum Dis, vol.72, pp.2018-2041, 2013.

M. Truchetet, B. Demoures, E. Guimaraes, J. Bertrand, A. Laurent et al., Platelets induce Thymic stromal Lymphopoietin production by endothelial cells: contribution to fibrosis in human systemic sclerosis, Arthritis Rheumatol, vol.68, pp.2784-94, 2016.

M. Scherlinger, Autoimmunity Reviews, vol.17, pp.625-635, 2018.

R. B. Christmann, A. Mathes, A. J. Affandi, C. Padilla, B. Nazari et al., Thymic stromal lymphopoietin is up-regulated in the skin of patients with systemic sclerosis and induces profibrotic genes and intracellular signaling that overlap with those induced by interleukin-13 and transforming growth factor ?, Arthritis Rheum, vol.65, pp.1335-1381, 2013.

M. Galindo, G. E. Martinez-vidal, M. P. Montes, S. Redondo, N. Santiago et al., Immunohistochemical detection of intravascular platelet microthrombi in patients with lupus nephritis and anti-phospholipid antibodies, Rheumatology, vol.48, pp.1003-1010, 2009.

E. Gonzalo, O. Toldos, M. P. Martínez-vidal, M. C. Ordoñez, B. Santiago et al., Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis, Arthritis Res Ther, vol.14, p.126, 2012.

N. Bose, A. Chiesa-vottero, and S. Chatterjee, Scleroderma renal crisis. Semin Arthritis Rheum, vol.44, pp.687-94, 2015.

T. Jin, K. Almehed, and H. Carlsten, Forsblad-d'Elia H. Decreased serum levels of TGF-?1 are associated with renal damage in female patients with systemic lupus erythematosus, Lupus, vol.21, pp.310-318, 2012.

T. Wu, C. Xie, H. W. Wang, X. J. Zhou, N. Schwartz et al., Elevated urinary VCAM-1, P-selectin, soluble TNF Receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis, J Immunol, vol.179, pp.7166-75, 2007.

G. Lu, R. Xu, S. Zhang, Q. Qiao, L. Shen et al., Alteration of circulatory platelet microparticles and endothelial microparticles in patients with chronic kidney disease, Int J Clin Exp Med, vol.8, p.16704, 2015.

Y. Yuan, M. Yang, K. Wang, J. Sun, L. Song et al., Excessive activation of the TLR9/TGF-?1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus, Arthritis Res Ther, vol.19, p.70, 2017.

A. Becker-merok, G. Ø. Eilertsen, and J. C. Nossent, Levels of transforming growth factorbeta are low in systemic lupus erythematosus patients with active disease, J Rheumatol, vol.37, pp.2039-2084, 2010.

Y. Delmas, J. Viallard, A. Solanilla, J. Villeneuve, J. Pasquet et al., Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40, Kidney Int, vol.68, pp.2068-78, 2005.

A. M. Hammad, H. M. Youssef, and M. M. El-arman, Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis, Lupus, vol.15, pp.608-620, 2006.

T. Tanaka, Human platelets stimulate mesangial cells to produce monocyte chemoattractant Protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury, J Am Soc Nephrol, vol.13, pp.2488-96, 2002.

G. Ruiz-irastorza, M. Egurbide, J. Pijoan, M. Garmendia, I. Villar et al., Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus, Lupus, vol.15, pp.577-83, 2006.

C. Bruni, E. Praino, S. Guiducci, S. Bellando-randone, D. E. Furst et al., Hydroxychloroquine and joint involvement in systemic sclerosis: preliminary beneficial results from a retrospective case-control series of an EUSTAR center, Joint Bone Spine, vol.84, pp.747-755, 2017.

R. G. Espinola, S. S. Pierangeli, A. E. Gharavi, E. N. Harris, and A. E. Ghara, Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies, Thromb Haemost, vol.87, pp.518-540, 2002.

C. Prowse, D. Pepper, and J. Dawes, Prevention of the platelet alpha-granule release reaction by membrane-active drugs, Thromb Res, vol.25, pp.219-246, 1982.

S. Achuthan, J. Ahluwalia, N. Shafiq, A. Bhalla, A. Pareek et al., Hydroxychloroquine's efficacy as an antiplatelet agent study in healthy volunteers: a proof of concept study, J Cardiovasc Pharmacol Ther, vol.20, pp.174-80, 2015.

D. Ferro, S. Basili, S. Roccaforte, D. Franco, M. Cipollone et al., Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus, Arthritis Rheum, vol.42, pp.2689-97, 1999.

I. Avalos, C. P. Chung, A. Oeser, G. L. Milne, H. Borntrager et al., Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus, Lupus, vol.16, pp.981-987, 2007.

G. Lessiani, N. Vazzana, C. Cuccurullo, D. Michele, D. Laurora et al., Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost, Thromb Haemost, vol.105, pp.321-329, 2011.

J. R. Kappa, M. K. Horn, C. A. Fisher, E. D. Cottrell, N. Ellison et al., Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations, J Thorac Cardiovasc Surg, vol.94, pp.405-418, 1987.

G. Xin, Z. Wei, C. Ji, H. Zheng, J. Gu et al., Metformin uniquely prevents thrombosis by inhibiting platelet activation and mtDNA release, Sci Rep, vol.6, 2016.

H. Wang, T. Li, S. Chen, Y. Gu, and S. Ye, Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin: NET mtDNA and metformin in SLE, Arthritis Rheum, vol.67, pp.3190-200, 2015.

C. Chamberlain, P. J. Colman, A. M. Ranger, L. C. Burkly, G. I. Johnston et al., Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles, Ann Rheum Dis, vol.76, pp.1837-1881, 2017.

D. T. Boumpas, R. Furie, S. Manzi, G. G. Illei, D. J. Wallace et al., A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis, Arthritis Rheum, vol.48, pp.719-746, 2003.

G. C. Tsokos, Systemic lupus erythematosus, N. Engl. J. Med, vol.365, pp.2110-2121, 2011.

E. Lazaro, M. Scherlinger, M. Truchetet, L. Chiche, T. Schaeverbeke et al., Biotherapies in systemic lupus erythematosus: New targets, vol.84, pp.267-274, 2017.

K. Ohl and K. Tenbrock, Regulatory T cells in systemic lupus erythematosus, Eur. J. Immunol, vol.45, pp.344-355, 2015.

C. Jacquemin, N. Schmitt, C. Contin-bordes, Y. Liu, P. Narayanan et al.,

V. Coffman, H. Pascual, P. Ueno, and . Blanco, OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response, vol.42, pp.1159-1170, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02962041

L. Pattarini, C. Trichot, S. Bogiatzi, M. Grandclaudon, S. Meller et al., TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand, J. Exp. Med, vol.214, pp.1529-1546, 2017.

C. Jacquemin, J. Augusto, M. Scherlinger, N. Gensous, E. Forcade et al.,

J. Pellegrin, T. Viallard, V. Schaeverbeke, C. Pascual, P. Contin-bordes et al., OX40L/OX40 axis impairs follicular and natural Treg function in human SLE, JCI Insight, vol.3, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02874595

O. Olumuyiwa-akeredolu, M. J. Page, P. Soma, and E. Pretorius, Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis, Nat. Rev. Rheumatol, vol.15, pp.237-248, 2019.

M. Scherlinger, V. Guillotin, M. Truchetet, C. Contin-bordes, V. Sisirak et al., Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets, Autoimmun. Rev, vol.17, pp.625-635, 2018.

P. Duffau, J. Seneschal, C. Nicco, C. Richez, E. Lazaro et al.,

C. Viallard, J. Goulvestre, B. Pellegrin, J. Weil, F. Moreau et al., Platelet CD154 Potentiates Interferon-Secretion by Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus, vol.2, pp.47-63, 2010.

G. I. Johnston, G. A. Bliss, P. J. Newman, and R. P. Mcever, Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of adhesion receptors for leukocytes, J. Biol. Chem, vol.265, pp.21381-21385, 1990.

S. J. Bielinski, C. Berardi, P. A. Decker, P. S. Kirsch, N. B. Larson et al.,

. Tsai, P-selectin and subclinical and clinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA), Atherosclerosis, vol.240, pp.3-9, 2015.

N. I. Shapiro, P. Schuetz, K. Yano, M. Sorasaki, S. M. Parikh et al., The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis, Crit. Care, vol.14, p.182, 2010.

M. Tsokos, F. Fehlauer, and K. Püschel, Immunohistochemical expression of E-selectin in sepsis-induced lung injury, Int. J. Legal Med, vol.113, pp.338-342, 2000.

M. Silva, R. K. Fung, C. B. Donnelly, P. A. Videira, and R. Sackstein, Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology, J. Immunol, vol.198, pp.3576-3587, 2017.

R. J. Johnston, L. J. Su, J. Pinckney, D. Critton, E. Boyer et al., VISTA is an acidic pH-selective ligand for PSGL-1, Nature, vol.574, pp.565-570, 2019.

R. Tinoco, F. Carrette, M. L. Barraza, D. C. Otero, J. Magaña et al.,

L. M. Swain and . Bradley, PSGL-1 is an immune checkpoint regulator that promotes T cell exhaustion, Immunity, vol.44, pp.1190-1203, 2016.

M. Miyara, D. Chader, E. Sage, D. Sugiyama, H. Nishikawa et al., Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3 high regulatory T cells in humans, Proc. Natl. Acad. Sci, vol.112, pp.7225-7230, 2015.

K. I. Hidari, A. S. Weyrich, G. A. Zimmerman, and R. P. Mcever, Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils, J. Biol. Chem, vol.272, pp.28750-28756, 1997.

A. Urzainqui, J. M. Serrador, F. Viedma, M. Yáñez-mó, A. Rodr??uez et al., ITAM-Based Interaction of ERM Proteins with Syk Mediates Signaling by the Leukocyte Adhesion Receptor PSGL-1, vol.17, pp.401-412, 2002.

A. Mócsai, J. Ruland, and V. L. Tybulewicz, The SYK tyrosine kinase: a crucial player in diverse biological functions, Nat. Rev. Immunol, vol.10, pp.387-402, 2010.

L. Sun, H. Jin, and H. Li, GARP: a surface molecule of regulatory T cells that is involved in the regulatory function and TGF-? releasing, Oncotarget, vol.7, pp.42826-42836, 2016.

T. Wu, C. Xie, H. W. Wang, X. J. Zhou, N. Schwartz et al., Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis, J. Immunol. Baltim. Md, vol.179, pp.7166-7175, 1950.

V. Sisirak, B. Sally, V. D'agati, W. Martinez-ortiz, Z. B. Özçakar et al.,

. Reizis, Apoptotic Cell Microparticles Prevents Autoimmunity, vol.166, pp.88-101, 2016.

A. Oyler-yaniv, J. Oyler-yaniv, B. M. Whitlock, Z. Liu, R. N. Germain et al., A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System, Immunity, vol.46, pp.609-620, 2017.

W. Li, C. Deng, H. Yang, and G. Wang, The Regulatory T Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-Analysis, Front. Immunol, vol.10, 2019.

X. Pan, X. Yuan, Y. Zheng, W. Wang, J. Shan et al., Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus, PLoS ONE, vol.7, 2012.

J. Y. Humrich, C. Spee-mayer, E. Siegert, M. Bertolo, A. Rose et al., Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial, Lancet Rheumatol, vol.1, pp.44-54, 2019.

M. Rosenzwajg, R. Lorenzon, P. Cacoub, H. P. Pham, F. Pitoiset et al., Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial, Ann. Rheum. Dis, vol.78, pp.209-217, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-01980090

K. Nakatani, H. Fujii, H. Hasegawa, M. Terada, N. Arita et al.,

K. Takahashi, S. Saiga, M. Yoshimoto, H. Iwano, Y. Shiiki et al., Endothelial adhesion molecules in glomerular lesions: Association with their severity and diversity in lupus models, Kidney Int, vol.65, pp.1290-1300, 2004.

A. Urzainqui, G. Del-hoyo, A. Lamana, H. De-la-fuente, O. Barreiro et al., Functional role of P-selectin glycoprotein ligand 1/P-selectin interaction in the generation of tolerogenic dendritic cells, J. Immunol. Baltim. Md, vol.179, pp.7457-7465, 1950.

J. Etulain, K. Martinod, S. L. Wong, S. M. Cifuni, M. Schattner et al., P-selectin promotes neutrophil extracellular trap formation in mice, Blood, vol.126, pp.242-246, 2015.

J. Suzuki, E. Hamada, T. Shodai, G. Kamoshida, S. Kudo et al., Cytokine Secretion from Human Monocytes Potentiated by P-Selectin-Mediated Cell Adhesion, Int. Arch. Allergy Immunol, vol.160, pp.152-160, 2013.

E. Boilard, P. A. Nigrovic, K. Larabee, G. F. Watts, J. S. Coblyn et al.,

M. Massarotti, E. Remold-o'donnell, R. W. Farndale, J. Ware, and D. M. Lee, Platelets amplify inflammation in arthritis via collagen-dependent microparticle production, Science, vol.327, pp.580-583, 2010.

P. Linge, P. R. Fortin, C. Lood, A. A. Bengtsson, and E. Boilard, The non-haemostatic role of platelets in systemic lupus erythematosus, Nat. Rev. Rheumatol, vol.14, pp.195-213, 2018.

M. Mezger, H. Nording, R. Sauter, T. Graf, C. Heim et al., Platelets and Immune Responses During Thromboinflammation, Front. Immunol, vol.10, 2019.

M. Giannelou and C. P. Mavragani, Cardiovascular disease in systemic lupus erythematosus: A comprehensive update, J. Autoimmun, vol.82, pp.1-12, 2017.

B. J. Skaggs, B. H. Hahn, and M. Mcmahon, Accelerated atherosclerosis in patients with SLE-mechanisms and management, Nat. Rev. Rheumatol, vol.8, pp.214-223, 2012.

D. E. Gaddis, L. E. Padgett, R. Wu, C. Mcskimming, V. Romines et al., Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis, Nat. Commun, vol.9, 2018.

P. C. Burger and D. D. Wagner, Platelet P-selectin facilitates atherosclerotic lesion development, Blood, vol.101, pp.2661-2666, 2003.

K. I. Ataga, A. Kutlar, J. Kanter, D. Liles, R. Cancado et al., Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease, N. Engl. J. Med, vol.376, pp.429-439, 2017.

N. Arraud, R. Linares, S. Tan, C. Gounou, J. Pasquet et al., Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration, J. Thromb. Haemost, vol.12, pp.614-627, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00996592

G. C. Tsokos, Systemic lupus erythematosus, N Engl J Med, vol.365, issue.22, pp.2110-2121, 2011.

K. Franklyn, A. Hoi, M. Nikpour, and E. F. Morand, The need to define treatment goals for systemic lupus erythematosus, Nat Rev Rheumatol, vol.10, issue.9, pp.567-571, 2014.

P. Blanco, A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau, Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus, Science, vol.294, issue.5546, pp.1540-1543, 2001.

P. Blanco, A. K. Palucka, V. Pascual, and J. Banchereau, Dendritic cells and cytokines in human inflammatory and autoimmune diseases, Cytokine Growth Factor Rev, vol.19, issue.1, pp.41-52, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00275657

D. J. Campbell and M. A. Koch, Phenotypical and functional specialization of FOXP3+ regulatory T cells, Nat Rev Immunol, vol.11, issue.2, pp.119-130, 2011.

K. J. Scalapino, Q. Tang, J. A. Bluestone, M. L. Bonyhadi, and D. I. Daikh, Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells, J Immunol, vol.177, issue.3, pp.1451-1459, 2006.

K. Ohl and K. Tenbrock, Regulatory T cells in systemic lupus erythematosus, Eur J Immunol, vol.45, issue.2, pp.344-355, 2015.

X. Valencia, C. Yarboro, G. Illei, and P. E. Lipsky, Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus, J Immunol, vol.178, issue.4, pp.2579-2588, 2007.

M. Miyara, Global natural regulatory T cell depletion in active systemic lupus erythematosus, J Immunol, vol.175, issue.12, pp.8392-8400, 2005.

B. Alvarado-sánchez, Regulatory T cells in patients with systemic lupus erythematosus, J Autoimmun, vol.27, issue.2, pp.110-118, 2006.

A. Golding, S. Hasni, G. Illei, and E. M. Shevach, The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus, Arthritis Rheum, vol.65, issue.11, pp.2898-2906, 2013.

T. Alexander, Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus, Ann Rheum Dis, vol.72, issue.9, pp.1549-1558, 2013.

M. A. Linterman, Foxp3+ follicular regulatory T cells control the germinal center response, Nat Med, vol.17, issue.8, pp.975-982, 2011.

Y. Chung, Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions, Nat Med, vol.17, issue.8, pp.983-988, 2011.

A. C. Grammer, Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions, J Clin Invest, vol.112, issue.10, pp.1506-1520, 2003.

C. Jacquemin, OX40 ligand contributes to human lupus pathogenesis by promoting T follicular helper response, Immunity, vol.42, issue.6, pp.1159-1170, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02962041

P. Blanco, H. Ueno, and N. Schmitt, T follicular helper (Tfh) cells in lupus: activation and involvement in SLE pathogenesis, Eur J Immunol, vol.46, issue.2, pp.281-290, 2016.

K. S. Voo, Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function, J Immunol, vol.191, issue.7, pp.3641-3650, 2013.

R. K. Venigalla, CD25-T cell sensitivity to the suppressive function of CD4+,CD25high,CD127 -/low regulatory T cells in patients with active systemic lupus erythematosus, Arthritis Rheum, vol.4, issue.7, pp.2120-2130, 2008.

X. Chen, R. Hamano, J. J. Subleski, A. A. Hurwitz, O. M. Howard et al., Expression of costimulatory TNFR2

. R-e-s-e-a-r-c-h-a-r-t-i-c-l-e, induces resistance of CD4+FoxP3-conventional T cells to suppression by CD4+FoxP3+ regulatory T cells, J Immunol, vol.185, issue.1, pp.174-182, 2010.

J. Y. Humrich, Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus, Proc Natl Acad Sci, vol.107, issue.1, pp.204-209, 2010.

L. Kastner, D. Dwyer, and F. X. Qin, Synergistic effect of IL-6 and IL-4 in driving fate revision of natural Foxp3+ regulatory T cells, J Immunol, vol.185, issue.10, pp.5778-5786, 2010.

Y. P. Rubtsov, Stability of the regulatory T cell lineage in vivo, Science, vol.329, issue.5999, pp.1667-1671, 2010.

P. T. Sage and A. H. Sharpe, T follicular regulatory cells in the regulation of B cell responses, Trends Immunol, vol.36, issue.7, pp.410-418, 2015.

S. Sakaguchi, D. A. Vignali, A. Y. Rudensky, R. E. Niec, and H. Waldmann, The plasticity and stability of regulatory T cells, Nat Rev Immunol, vol.13, issue.6, pp.461-467, 2013.

N. Komatsu, Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis, Nat Med, vol.20, issue.1, pp.62-68, 2014.

X. Zhou, Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo, Nat Immunol, vol.10, issue.9, pp.1000-1007, 2009.

A. Spence, J. E. Klementowicz, J. A. Bluestone, and Q. Tang, Targeting Treg signaling for the treatment of autoimmune diseases, Curr Opin Immunol, vol.37, pp.11-20, 2015.

D. Comte, Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus, Proc Natl Acad Sci, vol.113, issue.33, pp.9321-9326, 2016.

C. E. Ruby, Cutting Edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right, J Immunol, vol.183, issue.8, pp.4853-4857, 2009.

A. Gopisetty, OX40L/Jagged1 cosignaling by GM-CSF-induced bone marrow-derived dendritic cells is required for the expansion of functional regulatory T cells, J Immunol, vol.190, issue.11, pp.5516-5525, 2013.

H. Ueno, T follicular helper cells in human autoimmunity, Curr Opin Immunol, vol.43, pp.24-31, 2016.

N. Schmitt and H. Ueno, Human T follicular helper cells: development and subsets, Adv Exp Med Biol, vol.785, pp.87-94, 2013.

M. E. Truchetet, Platelets induce thymic stromal lymphopoietin production by endothelial cells: contribution to fibrosis in human systemic sclerosis, Arthritis Rheumatol, vol.68, issue.11, pp.2784-2794, 2016.

. Iv)-references,

L. Arnaud, J. Fagot, A. Mathian, M. Paita, A. Fagot-campagna et al., Prevalence and incidence of systemic lupus erythematosus in France: A 2010 nation-wide population-based study, Autoimmun. Rev, vol.13, pp.1082-1089, 2014.

M. Hermansen, J. Lindhardsen, C. Torp-pedersen, M. Faurschou, and S. Jacobsen, The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study, Rheumatol. Oxf. Engl, vol.56, pp.709-715, 2017.

S. Bernatsky, J. Boivin, L. Joseph, S. Manzi, E. Ginzler et al., Arthritis Rheum, vol.54, pp.2550-2557, 2006.

L. Arnaud, P. E. Gavand, R. Voll, A. Schwarting, F. Maurier et al., Predictors of fatigue and severe fatigue in a large international cohort of patients with systemic lupus erythematosus and a systematic review of the literature, Rheumatology, 2018.

E. Lazaro, M. Scherlinger, M. Truchetet, L. Chiche, T. Schaeverbeke et al., Biotherapies in systemic lupus erythematosus: New targets, vol.84, pp.267-274, 2017.

E. F. Morand, R. Furie, Y. Tanaka, I. N. Bruce, A. D. Askanase et al., Trial of Anifrolumab in Active Systemic Lupus Erythematosus, vol.382, pp.211-221, 2020.

D. Deafen, A. Escalante, L. Weinrib, D. Horwitz, B. Bachman et al., A revised estimate of twin concordance in systemic lupus erythematosus, Arthritis Rheum, vol.35, pp.311-318, 1992.

S. R. Block, J. B. Winfield, M. D. Lockshin, W. A. Angelo, and C. L. Christian, Studies of twins with systemic lupus erythematosus: A review of the literature and presentation of 12 additional sets, Am. J. Med, vol.59, pp.533-552, 1975.

R. R. Graham, G. Hom, W. Ortmann, and T. W. Behrens, Review of recent genome-wide association scans in lupus, J. Intern. Med, vol.265, pp.680-688, 2009.

O. J. Rullo and B. P. Tsao, Recent insights into the genetic basis of systemic lupus erythematosus, Ann. Rheum. Dis, vol.72, pp.56-61, 2013.

M. Cutolo, A. Sulli, B. Seriolo, S. Accardo, and A. T. Masi, Estrogens, the immune response and autoimmunity, vol.13, pp.217-226, 1995.

C. M. Syrett, B. Paneru, D. Sandoval-heglund, J. Wang, S. Banerjee et al., Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases, JCI Insight, vol.4, 2019.

R. H. Scofield, G. R. Bruner, B. Namjou, R. P. Kimberly, R. Ramsey-goldman et al.,

L. M. Alarcon, J. Vila, B. Reid, S. Harris, J. A. Li et al., Klinefelter's Syndrome, 47,XXY, in Male Systemic Lupus Erythematosus Supports a Gene Dose Effect from the X Chromosome, Arthritis Rheum, vol.58, pp.2511-2517, 2008.

C. M. Cooney, G. R. Bruner, T. Aberle, B. Namjou-khales, L. K. Myers et al., X,del(X)(q13) Turner's syndrome women with systemic lupus erythematosus in a pedigree multiplex for SLE, Genes Immun, vol.46, pp.478-481, 2009.

W. P. Lefeber, D. A. Norris, S. R. Ryan, J. C. Huff, L. A. Lee et al., Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes, J. Clin. Invest, vol.74, pp.1545-1551, 1984.

M. Barbhaiya, S. K. Tedeschi, B. Lu, S. Malspeis, D. Kreps et al., Cigarette Smoking and the Risk of Systemic Lupus Erythematosus, Overall and by Anti-Double Stranded DNA Antibody Subtype, in the Nurses' Health Study Cohorts, Ann. Rheum. Dis, vol.77, pp.196-202, 2018.

L. Arnaud, P. Mertz, P. Gavand, T. Martin, F. Chasset et al., Drug-induced systemic lupus: revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database, Ann. Rheum. Dis, vol.78, pp.504-508, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02153897

R. K. Gershon and K. Kondo, Cell interactions in the induction of tolerance: the role of thymic lymphocytes, Immunology, vol.18, p.723, 1970.

S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25), J. Immunol, vol.155, pp.1151-1164, 1995.

D. Dieckmann, H. Plottner, S. Berchtold, T. Berger, and G. Schuler, Ex Vivo Isolation and Characterization of Cd4+Cd25+ T Cells with Regulatory Properties from Human Blood, J. Exp. Med, vol.193, pp.1303-1310, 2001.

S. Hori, Control of Regulatory T Cell Development by the Transcription Factor Foxp3, Science, vol.299, pp.1057-1061, 2003.

M. E. Brunkow, E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark et al., Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse, Nat. Genet, vol.27, pp.68-73, 2001.

J. Huehn and M. Beyer, Epigenetic and transcriptional control of Foxp3+ regulatory T cells, Semin. Immunol, vol.27, pp.10-18, 2015.

Y. Zheng, S. Josefowicz, A. Chaudhry, X. P. Peng, K. Forbush et al., Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate, Nature, vol.463, pp.808-812, 2010.

H. Kim and W. J. Leonard, CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation, J. Exp. Med, vol.204, pp.1543-1551, 2007.

N. Ohkura, M. Hamaguchi, H. Morikawa, K. Sugimura, A. Tanaka et al., T Cell Receptor Stimulation-Induced Epigenetic Changes and Foxp3 Expression Are Independent and Complementary Events Required for Treg Cell Development, Immunity, vol.37, pp.785-799, 2012.

J. Van-loosdregt, Y. Vercoulen, T. Guichelaar, Y. Y. Gent, J. M. Beekman et al., Regulation of Treg functionality by acetylationmediated Foxp3 protein stabilization, Blood, vol.115, pp.965-974, 2010.

H. Kim, R. A. Barnitz, T. Kreslavsky, F. D. Brown, H. Moffett et al., Stable inhibitory activity of regulatory T cells requires the transcription factor Helios, vol.350, pp.334-339, 2015.

U. Baron, S. Floess, G. Wieczorek, K. Baumann, A. Grützkau et al., DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells, Eur. J. Immunol, vol.37, pp.2378-2389, 2007.

M. Miyara, Y. Yoshioka, A. Kitoh, T. Shima, K. Wing et al., Functional Delineation and Differentiation Dynamics of Human CD4+ T Cells Expressing the FoxP3 Transcription Factor, vol.30, pp.899-911, 2009.

M. Miyara, D. Chader, E. Sage, D. Sugiyama, H. Nishikawa et al., Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3 high regulatory T cells in humans, Proc. Natl. Acad. Sci, vol.112, pp.7225-7230, 2015.

M. Martinez, M. Joffraud, S. Giraud, B. Baïsse, M. P. Bernimoulin et al., Regulation of PSGL-1 Interactions with L-selectin, P-selectin, and E-selectin ROLE OF HUMAN FUCOSYLTRANSFERASE-IV AND -VII, J. Biol. Chem, vol.280, pp.5378-5390, 2005.

T. Ito, S. Hanabuchi, Y. Wang, W. R. Park, K. Arima et al., Two Functional Subsets of FOXP3+ Regulatory T Cells in Human Thymus and Periphery, vol.28, pp.870-880, 2008.

T. Duhen, R. Duhen, A. Lanzavecchia, F. Sallusto, and D. J. Campbell, Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells, Blood, vol.119, pp.4430-4440, 2012.

H. Qi, T follicular helper cells in space-time, Nat. Rev. Immunol, vol.16, pp.612-625, 2016.

M. A. Linterman, W. Pierson, S. K. Lee, A. Kallies, S. Kawamoto et al., Foxp3+ follicular regulatory T cells control T follicular helper cells and the germinal center response, Nat. Med, vol.17, pp.975-982, 2011.

Y. Chung, S. Tanaka, F. Chu, R. Nurieva, G. J. Martinez et al., Follicular regulatory T (Tfr) cells with dual Foxp3 and Bcl6 expression suppress germinal center reactions, Nat. Med, vol.17, pp.983-988, 2011.

X. Zhou, J. Tang, H. Cao, H. Fan, and B. Li, Tissue resident regulatory T cells: novel therapeutic targets for human disease, Cell. Mol. Immunol, vol.12, pp.543-552, 2015.

M. G. Roncarolo, S. Gregori, M. Battaglia, R. Bacchetta, K. Fleischhauer et al., Interleukin-10-secreting type 1 regulatory T cells in rodents and humans, Immunol. Rev, vol.212, pp.28-50, 2006.

K. Akane, S. Kojima, T. W. Mak, H. Shiku, and H. Suzuki, CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity, Proc. Natl. Acad. Sci, vol.113, pp.2460-2465, 2016.

S. Koizumi and H. Ishikawa, Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells, Cells, vol.8, p.939, 2019.

X. Zhou, S. Bailey-bucktrout, L. T. Jeker, C. Penaranda, M. Martínez-llordella et al.,

J. A. Rosenthal and . Bluestone, Foxp3 instability leads to the generation of pathogenic memory T cells in vivo, Nat. Immunol, vol.10, pp.1000-1007, 2009.

Y. P. Rubtsov, R. E. Niec, S. Josefowicz, L. Li, J. Darce et al., Stability of the regulatory T cell lineage in vivo, vol.329, pp.1667-1671, 2010.

B. Zhang, X. Zhang, F. Tang, L. Zhu, and Y. Liu, Reduction of forkhead box P3 levels in CD4+CD25high T cells in patients with new-onset systemic lupus erythematosus, vol.153, pp.182-187, 2008.

P. Laurent, V. Jolivel, P. Manicki, L. Chiu, C. Contin-bordes et al., Immune-Mediated Repair: A Matter of Plasticity, vol.8, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01673335

M. A. Koch, G. Tucker-heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl et al., The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation, Nat. Immunol, vol.10, pp.595-602, 2009.

Y. Zheng, A. Chaudhry, A. Kas, P. Deroos, J. M. Kim et al., Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses, Nature, vol.458, pp.351-356, 2009.

A. Chaudhry, D. Rudra, P. Treuting, R. M. Samstein, Y. Liang et al., CD4+ regulatory T cells control Th17 responses in a Stat3-dependent manner, vol.326, pp.986-991, 2009.

J. Hua, T. Inomata, Y. Chen, W. Foulsham, W. Stevenson et al., Pathological conversion of regulatory T cells is associated with loss of allotolerance, Sci. Rep, vol.8, pp.1-9, 2018.

A. K. Kannan, Z. Su, D. M. Gauvin, S. E. Paulsboe, R. Duggan et al.,

V. E. Mcgaraughty, S. B. Scott, and . Gauld, IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases, Sci. Rep, vol.9, pp.1-8, 2019.

S. Bhela, S. K. Varanasi, U. Jaggi, S. S. Sloan, N. K. Rajasagi et al., The Plasticity and Stability of Regulatory T Cells During Viral-Induced Inflammatory Lesions, J. Immunol. Baltim. Md, pp.1342-1352, 2017.

A. C. Foks, V. Frodermann, M. Borg, K. L. Habets, I. Bot et al., Differential effects of regulatory T cells on the initiation and regression of atherosclerosis, vol.218, pp.53-60, 2011.

D. E. Gaddis, L. E. Padgett, R. Wu, C. Mcskimming, V. Romines et al., Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis, Nat. Commun, vol.9, 2018.

T. Takahashi, Y. Kuniyasu, M. Toda, N. Sakaguchi, M. Itoh et al., Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state, Int. Immunol, vol.10, pp.1969-1980, 1998.

A. M. Thornton and E. M. Shevach, CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production, J. Exp. Med, vol.188, pp.287-296, 1998.

E. M. Shevach, Foxp3+ T Regulatory Cells: Still Many Unanswered Questions-A Perspective After 20 Years of Study, Front. Immunol, vol.9, 2018.

D. F. Fiorentino, M. W. Bond, and T. R. Mosmann, Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones, J. Exp. Med, vol.170, pp.2081-2095, 1989.

D. F. Fiorentino, A. Zlotnik, P. Vieira, T. R. Mosmann, M. Howard et al., Pillars Article: IL-10 Acts on the Antigen-presenting Cell to Inhibit Cytokine Production by Thl Cells, J. Immunol, vol.146, pp.1531-1538, 1991.

F. Rousset, E. Garcia, T. Defrance, C. Péronne, N. Vezzio et al., Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes, Proc. Natl. Acad. Sci, vol.89, pp.1890-1893, 1992.

R. Kühn, J. Löhler, D. Rennick, K. Rajewsky, and W. Müller, Interleukin-10-deficient mice develop chronic enterocolitis, Cell, vol.75, pp.263-274, 1993.

Y. P. Rubtsov, J. P. Rasmussen, E. Y. Chi, J. Fontenot, L. Castelli et al., Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces, vol.28, pp.546-558, 2008.

M. Murai, O. Turovskaya, G. Kim, R. Madan, C. L. Karp et al., Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis, Nat. Immunol, vol.10, pp.1178-1184, 2009.

?. A. Poniatowski, P. Wojdasiewicz, R. Gasik, and D. Szukiewicz, Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture Healing Biology and Potential Clinical Applications, Mediators Inflamm, 2015.

J. Cuende, S. Liénart, O. Dedobbeleer, J. Stockis, C. Huygens et al., Monoclonal antibodies against GARP/TGF-b1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo, p.12

J. C. Marie, J. J. Letterio, M. Gavin, and A. Y. Rudensky, TGF-?1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells, J. Exp. Med, vol.201, pp.1061-1067, 2005.

S. Fu, N. Zhang, A. C. Yopp, D. Chen, M. Mao et al., TGF-? Induces Foxp3 + T-Regulatory Cells from CD4 + CD25 ? Precursors, vol.4, pp.1614-1627, 2004.

S. A. Oh, M. Liu, B. G. Nixon, D. Kang, A. Toure et al., Foxp3-independent mechanism by which TGF-? controls peripheral T cell tolerance, Proc. Natl. Acad. Sci, vol.114, pp.7536-7544, 2017.

M. O. Li, Y. Y. Wan, and R. A. Flavell, T Cell-Produced Transforming Growth Factor-?1 Controls T Cell Tolerance and Regulates Th1-and Th17-Cell Differentiation, vol.26, pp.579-591, 2007.

L. W. Collison, C. J. Workman, T. T. Kuo, K. Boyd, Y. Wang et al., The inhibitory cytokine IL-35 contributes to regulatory T-cell function, Nature, vol.450, pp.566-569, 2007.

P. Shen, T. Roch, V. Lampropoulou, R. A. O'connor, U. Stervbo et al., IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases, Nature, vol.507, pp.366-370, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02639864

D. V. Sawant, H. Yano, M. Chikina, Q. Zhang, M. Liao et al., Adaptive plasticity of IL-10+ and IL-35+ Treg cells cooperatively promotes tumor T cell exhaustion, Nat. Immunol, vol.20, pp.724-735, 2019.

V. Chaturvedi, L. W. Collison, C. S. Guy, C. J. Workman, and D. A. Vignali, Cutting Edge: Human Regulatory T Cells Require IL-35 To Mediate Suppression and Infectious Tolerance, J. Immunol, vol.186, pp.6661-6666, 2011.

R. Palacios and G. Moller, T cell growth factor abrogates concanavalin A-induced suppressor cell function, J. Exp. Med, vol.153, pp.1360-1365, 1981.

P. Pandiyan, L. Zheng, S. Ishihara, J. Reed, and M. J. Lenardo, CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells, Nat. Immunol, vol.8, pp.1353-1362, 2007.

A. Oyler-yaniv, J. Oyler-yaniv, B. M. Whitlock, Z. Liu, R. N. Germain et al., A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System, Immunity, vol.46, pp.609-620, 2017.

T. Chinen, A. K. Kannan, A. G. Levine, X. Fan, U. Klein et al., An essential role for the IL-2 receptor in Treg cell function, Nat. Immunol, vol.17, pp.1322-1333, 2016.

W. G. Junger, Immune cell regulation by autocrine purinergic signalling, Nat. Rev. Immunol, vol.11, pp.201-212, 2011.

T. Woehrle, L. Yip, A. Elkhal, Y. Sumi, Y. Chen et al., Pannexin-1 hemichannelmediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse, Blood, vol.116, pp.3475-3484, 2010.

M. S. Alam, C. C. Kurtz, R. M. Rowlett, B. K. Reuter, E. Wiznerowicz et al., CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice, J. Infect. Dis, vol.199, pp.494-504, 2009.

M. Mandapathil, B. Hilldorfer, M. J. Szczepanski, M. Czystowska, M. Szajnik et al., Generation and Accumulation of Immunosuppressive Adenosine by Human CD4+CD25highFOXP3+ Regulatory T Cells, J. Biol. Chem, vol.285, pp.7176-7186, 2010.

S. Deaglio, K. M. Dwyer, W. Gao, D. Friedman, A. Usheva et al., Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression, J. Exp. Med, vol.204, pp.1257-1265, 2007.

A. Ohta, R. Kini, A. Ohta, M. Subramanian, M. Madasu et al., The development and immunosuppressive functions of CD4+ CD25+ FoxP3+ regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway, Front. Immunol, vol.3, 2012.

J. Challier, D. Bruniquel, A. K. Sewell, and B. Laugel, Adenosine and cAMP signalling skew human dendritic cell differentiation towards a tolerogenic phenotype with defective CD8+ T-cell priming capacity, Immunology, vol.138, pp.402-410, 2013.

A. Y. Wen, K. M. Sakamoto, and L. S. Miller, The Role of the Transcription Factor CREB in Immune Function, J. Immunol. Baltim. Md, vol.185, pp.6413-6419, 1950.

M. J. Loza, A. S. Anderson, K. S. O'rourke, J. Wood, and I. U. Khan, T -cell specific defect in expression of the NTPDase CD39 as a biomarker for lupus, Cell. Immunol, vol.271, pp.110-117, 2011.

L. Zhang, N. Yang, S. Wang, B. Huang, F. Li et al., Adenosine 2A receptor is protective against renal injury in MRL/lpr mice, 2010.

T. Yokosuka, W. Kobayashi, M. Takamatsu, K. Sakata-sogawa, H. Zeng et al., Spatiotemporal Basis of CTLA-4 Costimulatory Molecule-Mediated Negative Regulation of T Cell Activation, vol.33, pp.326-339, 2010.

T. Takahashi, T. Tagami, S. Yamazaki, T. Uede, J. Shimizu et al., Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyteassociated antigen 4, J. Exp. Med, vol.192, pp.303-310, 2000.

K. Wing, Y. Onishi, P. Prieto-martin, T. Yamaguchi, M. Miyara et al., CTLA-4 Control over Foxp3+ Regulatory T Cell Function, Science, vol.322, pp.271-275, 2008.

K. Murphy,

P. Travers and ;. Walport,

C. Janeway, Garland Science, ©2012

O. S. Qureshi, Y. Zheng, K. Nakamura, K. Attridge, C. Manzotti et al., Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4, Science, vol.332, pp.600-603, 2011.

L. S. Walker and D. M. Sansom, Confusing signals: Recent progress in CTLA-4 biology, Trends Immunol, vol.36, pp.63-70, 2015.

X. Tai, F. V. Laethem, L. Pobezinsky, T. Guinter, S. O. Sharrow et al., Basis of CTLA-4 function in regulatory and conventional CD4? T cells, vol.119, p.10, 2012.

C. Huang, C. J. Workman, D. Flies, X. Pan, A. L. Marson et al.,

J. D. Levitsky, D. M. Powell, C. G. Pardoll, D. A. Drake, and . Vignali, Role of LAG-3 in Regulatory T Cells, Immunity, vol.21, pp.503-513, 2004.

B. Liang, C. Workman, J. Lee, C. Chew, B. M. Dale et al., Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II, J. Immunol. Baltim. Md, vol.180, pp.5916-5926, 1950.

U. Grohmann, C. Orabona, F. Fallarino, C. Vacca, F. Calcinaro et al., CTLA-4-Ig regulates tryptophan catabolism in vivo, Nat. Immunol, vol.3, pp.1097-1101, 2002.

F. Fallarino, U. Grohmann, K. W. Hwang, C. Orabona, C. Vacca et al., Modulation of tryptophan catabolism by regulatory T cells, vol.4, pp.1206-1212, 2003.

M. Hill, S. Tanguy-royer, P. Royer, C. Chauveau, K. Asghar et al.,

M. Hubert, M. Heslan, L. Rimbert, J. R. Berthelot, R. Moffett et al., IDO expands human CD4+CD25high regulatory T cells by promoting maturation of LPS-treated dendritic cells, Eur. J. Immunol, vol.37, pp.3054-3062, 2007.

F. Fallarino, U. Grohmann, S. You, B. C. Mcgrath, D. R. Cavener et al.,

C. Belladonna, P. Volpi, M. C. Santamaria, P. Fioretti, and . Puccetti, The Combined Effects of Tryptophan Starvation and Tryptophan Catabolites Down-Regulate T Cell Receptor ?-Chain and Induce a Regulatory Phenotype in Naive T Cells, J. Immunol, vol.176, pp.6752-6761, 2006.

B. Baban, P. R. Chandler, M. D. Sharma, J. Pihkala, P. A. Koni et al., IDO activates regulatory T cells and blocks their conversion into TH17-like T cells, J. Immunol. Baltim. Md, vol.183, pp.2475-2483, 1950.

W. J. Grossman, J. W. Verbsky, W. Barchet, M. Colonna, J. P. Atkinson et al., Human T Regulatory Cells Can Use the Perforin Pathway to Cause Autologous Target Cell Death, Immunity, vol.21, pp.589-601, 2004.

N. Iikuni, E. V. Lourenço, B. H. Hahn, and A. L. Cava, Cutting Edge: Regulatory T Cells Directly Suppress B Cells in Systemic Lupus Erythematosus, J. Immunol, vol.183, pp.1518-1522, 2009.

X. Cao, S. F. Cai, T. A. Fehniger, J. Song, L. I. Collins et al., Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance, Immunity, vol.27, pp.635-646, 2007.

X. Ren, F. Ye, Z. Jiang, Y. Chu, S. Xiong et al., Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4 + CD25 + regulatory T cells, Cell Death Differ, vol.14, pp.2076-2084, 2007.

M. R. Pillai, L. W. Collison, X. Wang, D. Finkelstein, J. E. Rehg et al., The Plasticity of Regulatory T Cell Function, J. Immunol, vol.187, pp.4987-4997, 2011.

Q. Tang, K. J. Henriksen, M. Bi, E. B. Finger, G. Szot et al., In Vitro-expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes, J. Exp. Med, vol.199, pp.1455-1465, 2004.

A. L. Putnam, N. Safinia, A. Medvec, M. Laszkowska, M. Wray et al., Clinical Grade Manufacturing of Human Alloantigen-Reactive Regulatory T Cells for Use in Transplantation: Clinical Grade Alloantigen-Reactive Tregs, Am. J. Transplant, vol.13, pp.3010-3020, 2013.

Q. Zhang, W. Lu, C. Liang, Y. Chen, H. Liu et al., Chimeric Antigen Receptor (CAR) Treg: A Promising Approach to Inducing Immunological Tolerance, Front. Immunol, vol.9, 2018.

M. A. Gavin, S. R. Clarke, E. Negrou, A. Gallegos, and A. Rudensky, Homeostasis and anergy of CD4 + CD25 + suppressor T cells in vivo, Nat. Immunol, vol.3, pp.33-41, 2002.

D. Bending, P. Prieto-martín, A. Paduraru, C. Ducker, E. Marzaganov et al., A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo, J. Cell Biol, vol.217, pp.2931-2950, 2018.

A. E. Moran, K. L. Holzapfel, Y. Xing, N. R. Cunningham, J. S. Maltzman et al., T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse, J. Exp. Med, vol.208, pp.1279-1289, 2011.

J. C. Vahl, C. Drees, K. Heger, S. Heink, J. C. Fischer et al.,

D. Schallenberg, M. Y. Rieß, T. Hein, B. Buch, A. Polic et al., Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool, vol.41, pp.722-736, 2014.

L. A. O'neill, R. J. Kishton, and J. , A guide to immunometabolism for immunologists, Nat. Rev. Immunol, vol.16, pp.553-565, 2016.

V. A. Gerriets, R. J. Kishton, A. G. Nichols, A. N. Macintyre, M. Inoue et al., Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation, J. Clin. Invest, vol.125, pp.194-207, 2015.

L. Berod, C. Friedrich, A. Nandan, J. Freitag, S. Hagemann et al., De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells, Nat. Med, vol.20, pp.1327-1333, 2014.

A. Sharabi and G. C. Tsokos, T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy, Nat. Rev. Rheumatol, 2020.

H. Chi, Regulation and function of mTOR signalling in T cell fate decisions, Nat. Rev. Immunol, vol.12, pp.325-338, 2012.

H. Zeng, S. Cohen, C. Guy, S. Shrestha, G. Neale et al., mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation, vol.45, pp.540-554, 2016.

R. Wang, C. P. Dillon, L. Z. Shi, S. Milasta, R. Carter et al., The Transcription Factor Myc Controls Metabolic Reprogramming upon T Lymphocyte Activation, Immunity, vol.35, pp.871-882, 2011.

M. Battaglia, A. Stabilini, B. Migliavacca, J. Horejs-hoeck, T. Kaupper et al., Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients, J. Immunol, vol.177, pp.8338-8347, 2006.

M. M. Mihaylova and R. J. Shaw, The AMPK signalling pathway coordinates cell growth, autophagy and metabolism, Nat. Cell Biol, vol.13, pp.1016-1023, 2011.

S. Agarwal, C. M. Bell, S. B. Rothbart, and R. G. Moran, AMP-activated Protein Kinase (AMPK) Control of mTORC1 Is p53-and TSC2-independent in Pemetrexed-treated Carcinoma Cells, J. Biol. Chem, vol.290, pp.27473-27486, 2015.

R. D. Michalek, V. A. Gerriets, S. R. Jacobs, A. N. Macintyre, N. J. Maciver et al., Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets, J. Immunol, vol.186, pp.3299-3303, 2011.

D. Cluxton, A. Petrasca, B. Moran, and J. M. Fletcher, Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis, vol.10, 2019.

M. J. Barnes, T. Griseri, A. M. Johnson, W. Young, F. Powrie et al., CTLA-4 promotes Foxp3 induction and regulatory T cell accumulation in the intestinal lamina propria, Mucosal Immunol, vol.6, pp.324-334, 2013.

X. Valencia, G. Stephens, R. Goldbach-mansky, M. Wilson, E. M. Shevach et al., TNF downmodulates the function of human CD4+CD25hi T-regulatory cells, vol.108, pp.253-261, 2006.

W. J. Housley, C. O. Adams, F. C. Nichols, L. Puddington, E. G. Lingenheld et al., Natural but Not Inducible Regulatory T Cells Require TNF-? Signaling for In Vivo Function, J. Immunol, vol.186, pp.6779-6787, 2011.

S. Yang, C. Xie, Y. Chen, J. Wang, X. Chen et al., Differential roles of TNF?-TNFR1 and TNF?-TNFR2 in the differentiation and function of CD4 + Foxp3 + induced Treg cells in vitro and in vivo periphery in autoimmune diseases, Cell Death Dis, vol.10, pp.1-13, 2019.

S. Srivastava, M. A. Koch, M. Pepper, and D. J. Campbell, Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection, J. Exp. Med, vol.211, pp.961-974, 2014.

B. J. O'sullivan, H. E. Thomas, S. Pai, P. Santamaria, Y. Iwakura et al., IL-1? Breaks Tolerance through Expansion of CD25+ Effector T Cells, J. Immunol, vol.176, pp.7278-7287, 2006.

A. Metidji, S. A. Rieder, D. D. Glass, I. Cremer, G. A. Punkosdy et al., IFN?/?R Signaling Promotes Regulatory T Cell Development and Function Under Stress Conditions, J. Immunol. Baltim. Md, pp.4265-4276, 2015.

D. Gómez-martín, M. Díaz-zamudio, J. C. Crispín, and J. Alcocer-varela, Interleukin 2 and systemic lupus erythematosus, Autoimmun. Rev, vol.9, pp.34-39, 2009.

T. Koga, K. Ichinose, M. Mizui, J. C. Crispín, and G. C. Tsokos, Calcium/Calmodulin-Dependent Protein Kinase IV Suppresses IL-2 Production and Regulatory T Cell Activity in Lupus, J. Immunol, vol.189, pp.3490-3496, 2012.

T. Koga, M. Mizui, N. Yoshida, K. Otomo, L. A. Lieberman et al., KN-93, an inhibitor of calcium/calmodulin-dependent protein kinase IV, promotes generation and function of Foxp3 + regulatory T cells in MRL/ lpr mice, Autoimmunity, vol.47, pp.445-450, 2014.

S. K. Lathrop, S. M. Bloom, S. M. Rao, K. Nutsch, C. Lio et al., Peripheral education of the immune system by colonic commensal microbiota, Nature, vol.478, pp.250-254, 2011.

N. Arpaia, C. Campbell, X. Fan, S. Dikiy, J. Van-der-veeken et al., Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation, Nature, vol.504, pp.451-455, 2013.

K. J. Scalapino, D. I. Daikh, D. Unutmaz, and E. , Suppression of Glomerulonephritis in NZB/NZW Lupus Prone Mice by Adoptive Transfer of Ex Vivo Expanded Regulatory T Cells, PLoS ONE, vol.4, p.6031, 2009.

J. Y. Humrich, C. Spee-mayer, E. Siegert, M. Bertolo, A. Rose et al., Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial, Lancet Rheumatol, vol.1, pp.44-54, 2019.

M. Rosenzwajg, R. Lorenzon, P. Cacoub, H. P. Pham, F. Pitoiset et al.,

. Klatzmann, Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial, Ann. Rheum. Dis, vol.78, pp.209-217, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-01980090

M. Era, M. L. Pauli, K. Remedios, K. Taravati, P. M. Sandova et al., Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus, vol.71, pp.431-440, 2019.

S. Lin, K. Chen, C. Lin, C. Kuo, Q. Ling et al., The quantitative analysis of peripheral blood FOXP3-expressing T cells in systemic lupus erythematosus and rheumatoid arthritis patients, Eur. J. Clin. Invest, vol.37, pp.987-996, 2007.

M. Miyara, Z. Amoura, C. Parizot, C. Badoual, K. Dorgham et al., Global Natural Regulatory T Cell Depletion in Active Systemic Lupus Erythematosus, J. Immunol, vol.175, pp.8392-8400, 2005.

K. Tselios, A. Sarantopoulos, I. Gkougkourelas, and P. Boura, CD4+CD25highFOXP3+ T regulatory cells as a biomarker of disease activity in systemic lupus erythematosus: a prospective study, p.10

S. Piantoni, F. Regola, A. Zanola, L. Andreoli, F. Dall'ara et al., Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes, Lupus, vol.27, pp.143-149, 2018.

W. Li, C. Deng, H. Yang, and G. Wang, The Regulatory T Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-Analysis, Front. Immunol, vol.10, 2019.

B. Franz, B. Fritzsching, A. Riehl, N. Oberle, C. Klemke et al., Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus, Arthritis Rheum, vol.56, pp.1910-1920, 2007.

A. Afeltra, A. Gigante, D. P. Margiotta, C. Taffon, R. Cianci et al., The involvement of T regulatory lymphocytes in a cohort of lupus nephritis patients: a pilot study, Intern. Emerg. Med, vol.10, pp.677-683, 2015.

B. Yan, S. Ye, G. Chen, M. Kuang, N. Shen et al., Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-?-producing antigen-presenting cells, Arthritis Rheum, vol.58, pp.801-812, 2008.

R. K. Venigalla, T. Tretter, S. Krienke, R. Max, V. Eckstein et al., Reduced CD4+,CD25? T cell sensitivity to the suppressive function of CD4+,CD25 high ,CD127 ?/low regulatory T cells in patients with active systemic lupus erythematosus, Arthritis Rheum, vol.58, pp.2120-2130, 2008.

M. Bonelli, A. Savitskaya, K. Dalwigk, C. W. Steiner, D. Aletaha et al., Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE), Int. Immunol, vol.20, pp.861-868, 2008.

D. Klatzmann and A. K. Abbas, The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases, Nat. Rev. Immunol, vol.15, pp.283-294, 2015.
URL : https://hal.archives-ouvertes.fr/inserm-01617541

S. David, R. Michelle, J. Florence, S. Adrien, C. Fabrice et al., Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis, N. Engl. J. Med, p.11, 2011.

J. He, X. Zhang, Y. Wei, X. Sun, Y. Chen et al., Low-dose interleukin-2 treatment selectively modulates CD4 + T cell subsets in patients with systemic lupus erythematosus, Nat. Med, vol.22, pp.991-993, 2016.

Z. Lai, R. Kelly, T. Winans, I. Marchena, A. Shadakshari et al., Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, The Lancet, vol.391, pp.1186-1196, 2018.

H. Son, J. Lee, S. Lee, E. Kim, M. Park et al., Metformin Attenuates Experimental Autoimmune Arthritis through Reciprocal Regulation of Th17/Treg Balance and Osteoclastogenesis, Mediators Inflamm, 2014.

Y. Yin, S. Choi, Z. Xu, D. J. Perry, H. Seay et al., Normalization of CD4+ T cell metabolism reverses lupus, Sci. Transl. Med, vol.7, pp.274-292, 2015.

F. Sun, H. J. Wang, Z. Liu, S. Geng, H. T. Wang et al., Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double-blind, placebocontrolled trial, Lancet Rheumatol, vol.2, pp.210-216, 2020.

J. A. Bluestone, J. H. Buckner, M. Fitch, S. E. Gitelman, S. Gupta et al., Type 1 diabetes immunotherapy using polyclonal regulatory T cells, vol.7, pp.315-189, 2015.

P. Duffau, J. Seneschal, C. Nicco, C. Richez, E. Lazaro et al.,

B. Pellegrin, J. Weil, F. Moreau, P. Batteux, and . Blanco, Platelet CD154 Potentiates Interferon-Secretion by Plasmacytoid Dendritic Cells in Systemic Lupus Erythematosus, vol.2, pp.47-63, 2010.

I. A. Andrianova, A. A. Ponomareva, E. R. Mordakhanova, G. L. Minh, A. G. Daminova et al., In systemic lupus erythematosus anti-dsDNA antibodies can promote thrombosis through direct platelet activation, J. Autoimmun, vol.107, p.102355, 2020.

J. E. Joseph, P. Harrison, I. J. Mackie, D. A. Isenberg, and S. J. Machin, Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis, Br. J. Haematol, vol.115, pp.451-459, 2001.

M. Koupenova, O. Vitseva, C. R. Mackay, L. M. Beaulieu, E. J. Benjamin et al., Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis, Blood, vol.124, pp.791-802, 2014.

M. Scherlinger, V. Sisirak, C. Richez, E. Lazaro, P. Duffau et al., New Insights on Platelets and Platelet-Derived Microparticles in Systemic Lupus Erythematosus, vol.19, p.48, 2017.

L. Bennett, A. K. Palucka, E. Arce, V. Cantrell, J. Borvak et al., Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood, J. Exp. Med, vol.197, pp.711-723, 2003.

E. C. Baechler, F. M. Batliwalla, G. Karypis, P. M. Gaffney, W. A. Ortmann et al., Kapur, others, Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus, Proc. Natl. Acad. Sci, vol.100, pp.2610-2615, 2003.

M. Nagahama, S. Nomura, Y. Ozaki, C. Yoshimura, H. Kagawa et al., Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus, Autoimmunity, vol.33, pp.85-94, 2001.

C. Lood, S. Amisten, B. Gullstrand, A. Jonsen, M. Allhorn et al., Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: upregulation of the type I interferon system is strongly associated with vascular disease, Blood, vol.116, pp.1951-1957, 2010.

C. Lood, H. Tydén, B. Gullstrand, C. T. Nielsen, N. H. Heegaard et al., Decreased platelet size is associated with platelet activation and anti-phospholipid syndrome in systemic lupus erythematosus, Rheumatology, p.437, 2016.

S. Nhek, R. Clancy, K. A. Lee, N. M. Allen, T. J. Barrett et al., Newman, others, Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1? Pathway in Systemic Lupus Erythematosus, Arterioscler. Thromb. Vasc. Biol, p.116, 2017.

G. Berger, D. W. Hartwell, D. D. Wagner, P. -selectin, and P. Clearance, Blood, vol.92, pp.4446-4452, 1998.

T. Wu, C. Xie, H. W. Wang, X. J. Zhou, N. Schwartz et al., Elevated Urinary VCAM-1, P-Selectin, Soluble TNF Receptor-1, and CXC Chemokine Ligand 16 in Multiple Murine Lupus Strains and Human Lupus Nephritis, J. Immunol, vol.179, pp.7166-7175, 2007.

V. Sisirak, B. Sally, V. D'agati, W. Martinez-ortiz, Z. B. Özçakar et al., Digestion of Chromatin in Apoptotic Cell Microparticles Prevents Autoimmunity, vol.166, pp.88-101, 2016.

R. A. Furie, E. F. Morand, I. N. Bruce, S. Manzi, K. C. Kalunian et al., Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, vol.1, pp.208-219, 2019.

S. Yang, Y. Lai, M. Huang, C. Tsai, and J. Wang, Corticosteroid dose and the risk of opportunistic infection in a national systemic lupus erythematosus cohort, Lupus, p.961203318792352, 2018.

F. Ballocca, F. D'ascenzo, C. Moretti, P. Omedè, E. Cerrato et al., Predictors of cardiovascular events in patients with systemic lupus erythematosus (SLE): a systematic review and meta-analysis, Eur. J. Prev. Cardiol, vol.22, pp.1435-1441, 2015.

S. J. Bielinski, C. Berardi, P. A. Decker, P. S. Kirsch, N. B. Larson et al., P-selectin and subclinical and clinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA), Atherosclerosis, vol.240, pp.3-9, 2015.

P. M. Ridker, J. E. Buring, and N. Rifai, Soluble P-Selectin and the Risk of Future Cardiovascular Events, Circulation, vol.103, pp.491-495, 2001.

P. C. Burger and D. D. Wagner, Platelet P-selectin facilitates atherosclerotic lesion development, Blood, vol.101, pp.2661-2666, 2003.

K. I. Ataga, A. Kutlar, J. Kanter, D. Liles, R. Cancado et al., Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease, N. Engl. J. Med, vol.376, pp.429-439, 2017.

L. Zhang, S. Chen, Y. Liu, X. Xu, Q. Zhang et al., P-selectin blockade ameliorates lupus nephritis in MRL/lpr mice through improving renal hypoxia and evaluation using BOLD-MRI, J. Transl. Med, vol.18, p.116, 2020.

J. Ara, E. Mirapeix, P. Arrizabalaga, R. Rodriguez, C. Ascaso et al., Circulating soluble adhesion molecules in ANCA-associated vasculitis, Nephrol. Dial. Transplant, vol.16, pp.276-285, 2001.

A. D. Blann, J. Constans, P. Carpentier, M. Renard, B. Satger et al., Soluble P selectin in systemic sclerosis: relationship with von Willebrand factor, autoantibodies and diffuse or localised/limited disease, Thromb. Res, vol.109, pp.203-206, 2003.

J. Berthelot, B. L. Goff, A. Neel, Y. Maugars, and M. Hamidou, NETosis: At the crossroads of rheumatoid arthritis, lupus, and vasculitis, Joint Bone Spine, vol.84, pp.255-262, 2017.

H. Wang, T. Li, S. Chen, Y. Gu, and S. Ye, Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin: NET mtDNA AND METFORMIN IN SLE, Arthritis Rheumatol, vol.67, pp.3190-3200, 2015.

J. Etulain, K. Martinod, S. L. Wong, S. M. Cifuni, M. Schattner et al., P-selectin promotes neutrophil extracellular trap formation in mice, Blood, vol.126, pp.242-246, 2015.

J. Perdomo, H. H. Leung, Z. Ahmadi, F. Yan, J. J. Chong et al., Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia, Nat. Commun, vol.10, p.1322, 2019.

P. Han, D. Hanlon, N. Arshad, J. S. Lee, K. Tatsuno et al., Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes, Sci. Adv, vol.6, p.1580, 2020.

R. Tinoco, F. Carrette, M. L. Barraza, D. C. Otero, J. Magaña et al., PSGL-1 is an immune checkpoint regulator that promotes T cell exhaustion, Immunity, vol.44, pp.1190-1203, 2016.

R. J. Johnston, L. J. Su, J. Pinckney, D. Critton, E. Boyer et al., VISTA is an acidic pHselective ligand for PSGL-1, Nature, vol.574, pp.565-570, 2019.

C. Jacquemin, N. Schmitt, C. Contin-bordes, Y. Liu, P. Narayanan et al., OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response, vol.42, pp.1159-1170, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02962041

. V)-annexes,

. Article-collaboratif-:-l'ascorbate, . Une, and . Plasmatique,

. Dans, Son équipe travaille sur le polynucléaire neutrophile et plus spécifiquement sur les interaction entre les pathogènes et l'environnement sur cette cellule

, Dans cette étude princeps, l'idée était d'évaluer l'état d'oxygénation des cellules dans le plasma

, Université de Bordeaux, IBGCUMR 5095, 1 rue Camille Saint Saëns, 33077 Bordeaux Cedex, France. 3 UMR-CNRS UMR -5164 Immunoconcept, 146 rue Léon Saignat, 33076 Bordeaux, France. 4 Faculty of Health and Medical Sciences, du sang veineux de 12 donneurs sains non-fumeurs a été prélevé, vol.9002, p.67000

, Blood samples were collected either in commercial collection tubes (BD Vacutainer K2E (EDTA), ref 368,861) or in Hypoxytubes developed in collaboration with the Greiner Bio One (GBO) company, containing a limited amount of O 2 . (tubes were sealed under a nitrogen atmosphere). Internal pO 2 was quantified in commercial tubes and in Hypoxytubes using, (0123456789) Scientific RepoRtS | (2020) 10:10659 |

, All participants gave written informed consent and all the study procedures were carried out in accordance with the Declaration of Helsinki principles. Human blood was collected from healthy patients at the ICAReB service of the Pasteur Institut (authorization No. 2020_0120), cell culture. HEK293T (ATCC CRL-1573) and Hep-G2 (ATCC HB-8065) were cultured in DMEM + 8%

, White blood cells (WBCs) were purified form whole blood in an anoxic chamber by the addition of a 6% dextran solution (30 min, RT). The WBC-containing supernatant was collected and resuspended in RPMI 1,640 (Thermofisher); remaining red blood cells were eliminated with a lysis buffer. Cells were fixed in paraformaldehyde (PFA) 3.3% for immunofluorescent labelling or labeled with fluorescent marker for flow cytometry analysis, as previously described 16 . plasma po 2 measurement and components' dosage. Immediately after blood collection, the plasma pO 2 was measured directly in the blood collection tube using an oximeter with a standardized microsensor equipped with a steel needle (Unisense), as previously described 17 . Following centrifugation for 5 min at 2,000×g, the plasma was acidified with an equal volume of 10% (w/v) metaphosphoric acid (MPA) containing 2 mmol/L of disodium-EDTA. Ascorbate concentration was quantified by high-performance liquid chromatography with coulometric detection, as described previously 18 . Likewise, using high-performance liquid chromatography with coulometric detection, ?-and ?-tocopherol were analyzed as described by Sattler et al. 19 , and ubiquinone and ubiquinol as described elsewhere 20, SVF. Cells were seeded onto 24-well plates and incubated 24 h at 37 °C at 0% (anoxic cabinet) or 21% O 2

, Immediately after blood collection, samples were centrifuged, and plasma fractions were loaded in closed cuves (2 mL). Oxygen consumption fluxes were assessed when reaching constant values. Experiments were conducted with fresh plasma and after oxidation (exposure to atmospheric air: at least 30 min on a rotator mixer, Plasma oxygen reduction rate quantification. Plasma oxygen consumption rate was measured with an oximeter (Oroboros O2k-FluoRespirometer)

, Invitrogen); nuclei with DAPI. Cell imaging was performed with a confocal microscope, Leica DM5500 TCS SPE). Flow cytometry. Cells were resuspended in PBS + 2 mM EDTA, labeled with 100 nM TMRM (T5428, Sigma-Aldrich) and analyzed with FACSCcalibur (BD Biosciences, vol.124, p.366

, Guinea pig plasma analysis. 3-week Dunkin-Hartley guinea pigs (Charles River) were fed for fifteen days with a standard diet (400 mg ascorbate/kg, Safediet ref. 106) or an ascorbate-deficient diet (< 50 mg ascorbate/ kg). Blood samples were collected in Hypoxytubes; plasma ascorbate concentration and pO 2 were determined as described above

R. N. Pittman, Regulation of tissue oxygenation, Colloq. Ser. Integr. Syst. Physiol. Mol. Funct, vol.3, pp.1-100, 2011.

K. M. Christmas and J. B. Bassingthwaighte, Equations for O2 and CO2 solubilities in saline and plasma: combining temperature and density dependences, J. Appl. Physiol. Bethesda Md, vol.122, 2017.

D. J. Vanderjagt, P. J. Garry, and W. C. Hunt, Ascorbate in plasma as measured by liquid chromatography and by dichlorophenolindophenol colorimetry, Clin. Chem, vol.32, pp.1004-1006, 1986.

J. Lykkesfeldt and P. Tveden-nyborg, The pharmacokinetics of vitamin C, Nutrients, vol.11, p.2412, 2019.

D. E. Cabelli and B. H. Bielski, Kinetics and mechanism for the oxidation of ascorbic acid/ascorbate by HO2/O2-(hydroperoxyl/ superoxide) radicals. A pulse radiolysis and stopped-flow photolysis study, J. Phys. Chem, vol.87, pp.1809-1812, 1983.

R. Fukuda, HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells, Cell, vol.129, pp.111-122, 2007.

H. Zhang, HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity, Cancer Cell, vol.11, pp.407-420, 2007.

, (1234567890) Scientific RepoRtS | (2020) 10:10659 |

I. Papandreou, R. A. Cairns, L. Fontana, A. L. Lim, and N. C. Denko, HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption, Cell Metab, vol.3, pp.187-197, 2006.

B. Frei, L. England, and B. N. Ames, Ascorbate is an outstanding antioxidant in human blood plasma, Proc. Natl. Acad. Sci, vol.86, pp.6377-6381, 1989.

H. Pu, H. Jiang, R. Chen, and H. Wang, Studies on the interaction between vincamine and human serum albumin: a spectroscopic approach, Lumin. J. Biol. Chem. Lumin, vol.29, pp.471-479, 2013.

S. J. Padayatty, Vitamin C pharmacokinetics: implications for oral and intravenous use, Ann. Intern. Med, vol.140, p.533, 2004.

Y. Li and H. E. Schellhorn, New developments and novel therapeutic perspectives for vitamin C, J. Nutr, vol.137, pp.2171-2184, 2007.

M. Minetti, Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation. No spin-trapping evidence for the hydroxyl radical in iron-overloaded plasma, Biochem. J, vol.282, pp.459-465, 1992.

J. G. Mohanty, E. Nagababu, and J. M. Rifkind, Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging, Front Physiol, vol.5, p.84, 2014.

K. Manasa and R. Vani, Influence of oxidative stress on stored platelets, Adv. Hematol, p.4091461, 2016.

V. Monceaux, Anoxia and glucose supplementation preserve neutrophil viability and function, Blood, vol.128, pp.993-1002, 2016.

J. Tinevez, Shigella-mediated oxygen depletion is essential for intestinal mucosa colonization, Nat. Microbiol, vol.4, 2001.
URL : https://hal.archives-ouvertes.fr/hal-02402067

J. Lykkesfeldt, Measurement of ascorbic acid and dehydroascorbic acid in biological samples, Curr. Protoc. Toxicol. Éditor Board Mahin D Maines Ed Et Al Chapter, pp.1-15, 2002.

W. Sattler, D. Mohr, and R. Stocker, Rapid isolation of lipoproteins and assessment of their peroxidation by high-performance liquid chromatography postcolumn chemiluminescence, Methods Enzymol, vol.233, pp.469-489, 1994.

A. M. Schou-pedersen, D. Schemeth, and J. Lykkesfeldt, Determination of reduced and oxidized coenzyme Q10 in canine plasma and heart tissue by HPLC-ECD: comparison with LC-MS/MS quantification, Antioxidants, vol.8, p.253, 2019.

. Donnees and . De, , vol.3, p.31

S. Figure, Recombinant sOX40L does not induce Treg cell death and Purified CD14+ 766 monocytes cultured in the presence of SLE sera (SLE-DC) or ex-vivo SLE-mDC expressed

, Sorted CD4 + CD25 + CD127 -Tregs cells were cultured with or without sOX40L (100 ng/mL) and

-. Annexin, /PI staining was performed after 3 days of culture for the assessment of cell death, p.771

, Annexin-V + /PI + cells were 772 considered as dead cells. (B), Cumulative data showing the percentage of dead cells after 3 days of 773 Tregs culture, Representative dot plot of Treg Annexin-V/PI staining after 3 days of culture

, Purified CD14 + monocytes from healthy donors were cultured with GM-CSF+IL-4 or SLE Sera (SLE

, Cumulative results for OX40L-expression (as expressed by MFI) in both 777 conditions, GM-CSF+IL-4 DC (n=8), SLE-DC (n=21). Cumulative data are shown with S.E.M and P 778 value < 0.01 (**). (E-F) Ex-vivo OX40L expression level was assessed within circulating APCs such as

+. Cd11c and . Dr-+-mdc, SLEDAI < 6) SLE) APCs were analyzed by 781 flow cytometry. The figure shows a representative staining and cumulative data represented as mean 782 with S.E.M. Data are compared using non parametric Mann-Whitney test, CD14+ monocytes and CD19+ B lymphocytes cells. 7 healthy donors and 15 SLE 780 patients (including 9 active (SLEDAI ? 6 and 7 quiescent

S. Figure, A) Effect of sOX40L on the proliferative capacity of Effector CD4+ T cells following activation with anti-789 CD3 and anti-CD28 at different concentrations. Purified CD4 T cells were stained with CFSE and 790 stimulated with or without agonist soluble OX40L (100ng/ml) for 4 days with different concentration of 791 pre-coated anti-CD3 and soluble anti-CD28, Effect of sOX40L on effector CD4 T cells proliferation alone 787, vol.788

, Effect of soluble OX40L (100ng/ml) co-stimulation on effector CD4 T cells proliferation stimulated by 793 anti-CD3 and anti-CD28 micro-beads

, Dose effect of soluble OX40L co-stimulation (100ng/ml) on purified effector CD4 T cells stimulated 795 by pre-coated anti-CD3 (1ug/ml) and soluble anti-CD28 (3ug/ml) or anti-CD3+anti-CD28 beads for 4 796 days, vol.4

S. Figure, Blood CD4 + CD25 high Tregs and serum concentration of sOX40L in healthy donors and 813 SLE patients

, A) Serum concentration of sOX40L (in ng/ml) from HD (n=15), iSLE (n=14) and aSLE patients (n=11)

, M, and compared using non-parametric Kruskall-Wallis 817 test with Dunn's correction for multiple comparisons, p.818

, Peripheral Effector CD4 T cells, Tregs, and B cells were investigated for OX40 820 expression by flow cytometry. PBMCs were isolated and stained for OX40 expression from Healthy 821 donors (n=8) and SLE patients (n=9). (C) Representative staining and (D) OX40 MFI values with S.E.M 822 are shown and compared using one-way ANOVA, Correlation between sOX40L concentration in serum and SLE activity (SLEDAI), using Spearman rank 819 correlation test. (C-D)

, 01 (**), p<0.0001 (****). (E), sOX40L impacts Foxp3 expression in different Treg subset

, ml) supplemented by soluble anti-CD28 (3ug/ml) in 96 wells plate for 3 days. Intra-nuclear Foxp3 826 expression was assessed by flow cytometry on different Treg sub-population based on CD25 and 827 CD45RA cell surface expression: active Tregs (CD45RA -CD25 high ), resting Tregs (CD45RA + CD25 + ) and 828 non-functional Tregs (CD45RA -CD25 + ) subset. 5 different donors were studied in 2 independent 829 experiments. Individual data are shown with mean and S.E.M, and compared using non-parametric two-830 tailed Mann-Whitney test, Frequency of blood CD4 + CD25 high Tregs in HD 831 (n=10) and SLE patients with inactive (iSLE, n=25)

, Kruskall-Wallis test with Dunn's correction for multiple comparisons

, Results are 835 expressed in Giga/L and are compared using non-parametric Kruskall-Wallis test with Dunn's correction 836 for multiple comparisons. iSLE, patients with inactive disease (SLEDAI<6); aSLE, CD4 + CD25 high Tregs cell in blood of HD (n=10) and iSLE (n=25) and aSLE patients (n=24)

S. Figure, Tregs intranuclear Helios expression following OX40L co-stimulation

, Intranuclear Helios expression level was evaluated 877 by flow cytometry. 9 independents experiments using 9 different Tregs donors were realized. Data are 878 shown as mean MFI and compared using two-tailed paired non-parametric Wilcoxon test, p.5