J. S. Bezbradica and R. Medzhitov, Integration of cytokine and heterologous receptor signaling pathways, Nat. Immunol, vol.10, pp.333-339, 2009.

C. Nathan and M. Sporn, Cytokines in context. J. Cell Biol, vol.113, pp.981-986, 1991.

J. J. Shea, C. D. Cells, and W. E. Paul, Commitment and plasticity of helper, Science, vol.327, pp.1098-1102, 2010.

L. Zhou, M. M. Chong, and D. R. Littman, Review plasticity of CD4 þ T cell lineage differentiation, Immunity, vol.30, pp.646-655, 2009.
DOI : 10.1016/j.immuni.2009.05.001
URL : https://doi.org/10.1016/j.immuni.2009.05.001

E. Borden, G. Sen, and G. Uze, Interferons at age 50: past, current and future impact on biomedicine, Nat. Rev. Drug Discov, vol.6, pp.975-990, 2007.
DOI : 10.1038/nrd2422
URL : https://hal.archives-ouvertes.fr/hal-00203077

Y. Mitsui and T. Senda, Elucidation of the basic three-dimensional structure of type I interferons and its functional and evolutionary implications, J. Interferon Cytokine Res, vol.17, pp.319-326, 1997.

A. N. Theofilopoulos, R. Baccala, B. Beutler, and D. H. Kono, Type I interferons (alpha/beta) in immunity and autoimmunity, Annu. Rev. Immunol, vol.23, pp.307-336, 2005.
DOI : 10.1146/annurev.immunol.23.021704.115843

G. Trinchieri, Type I interferon: friend or foe?, J. Exp. Med, vol.207, pp.2053-2063, 2010.

L. Bennett, Interferon and granulopoiesis signatures in systemic lupus erythematosus blood, J. Exp. Med, vol.197, pp.711-723, 2003.

M. P. Berry, An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis, Nature, vol.466, pp.973-977, 2010.

T. Decker, M. Muller, and S. Stockinger, The yin and yang of type I interferon activity in bacterial infection, Nat. Rev. Immunol, vol.5, pp.675-687, 2005.

K. M. Monroe, S. M. Mcwhirter, and R. E. Vance, Induction of type I interferons by bacteria, Cell Microbiol, vol.12, pp.881-890, 2010.

V. Pascual, A genomic approach to human autoimmune diseases, Annu. Rev. Immunol, vol.28, pp.535-571, 2010.

L. Ronnblom and M. L. Eloranta, The interferon signature in autoimmune diseases, Curr. Opin. Rheumatol, vol.25, pp.248-253, 2013.

E. Volpe, A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses, Nat. Immunol, vol.9, pp.650-657, 2008.

A. Doi,

, NATURE COMMUNICATIONS |, vol.5, p.3987

, All rights reserved

C. D. Krause and S. Pestka, Evolution of the Class 2 cytokines and receptors, and discovery of new friends and relatives, Pharmacol. Ther, vol.106, pp.299-346, 2005.

A. García-sastre and C. Biron, Type 1 interferons and the virus-host relationship: a lesson in detente, Science, vol.312, pp.879-882, 2006.

J. M. Brenchley, Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections, Blood, vol.112, pp.2826-2835, 2008.
DOI : 10.1182/blood-2008-05-159301
URL : http://www.bloodjournal.org/content/112/7/2826.full.pdf

A. Gosselin, Peripheral blood CCR4 þ CCR6 þ and CXCR3 þ CCR6 þ CD4 þ T cells are highly permissive to HIV-1 infection, J. Immunol, vol.184, pp.1604-1616, 2010.

J. Schoggins, S. Wilson, and M. Panis, A diverse range of gene products are effectors of the type I interferon antiviral response, Nature, vol.472, pp.481-485, 2011.

E. Esplugues, Control of TH17 cells occurs in the small intestine, Nature, vol.475, pp.514-518, 2011.

L. Rogge, D. D'ambrosio, and M. Biffi, The role of Stat4 in species-specific regulation of Th cell development by type I IFNs, J. Immunol, vol.161, pp.6567-6574, 1998.

J. Huber and H. Ramos, Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3, J. Immunol, vol.185, pp.813-817, 2010.

A. R. Moschen, S. Geiger, I. Krehan, A. Kaser, and H. Tilg, Interferon-alpha controls IL-17 expression in vitro and in vivo, Immunobiology, vol.213, pp.779-787, 2008.

M. Prinz, Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system, Immunity, vol.28, pp.675-686, 2008.

R. C. Axtell, T helper type 1 and 17 cells determine efficacy of interferonbeta in multiple sclerosis and experimental encephalomyelitis, Nat. Med, vol.16, pp.406-412, 2010.

M. T. Wong, Regulation of human Th9 differentiation by type I interferons and IL-21, Immunol. Cell. Biol, vol.88, pp.624-631, 2009.

N. Dikopoulos, Type I IFN negatively regulates CD8 þ T cell responses through IL-10-producing CD4 þ T regulatory 1 cells, J. Immunol, vol.174, pp.99-109, 2005.

T. Ichinohe, Microbiota regulates immune defense against respiratory tract influenza A virus infection, Proc. Natl Acad. Sci. USA, vol.108, pp.5354-5359, 2011.

M. Kane, Successful transmission of a retrovirus depends on the commensal microbiota, Science, vol.334, pp.245-249, 2011.

S. K. Kuss, Intestinal microbiota promote enteric virus replication and systemic pathogenesis, Science, vol.334, pp.249-252, 2011.

M. C. Abt, Commensal bacteria calibrate the activation threshold of innate antiviral immunity, Immunity, vol.37, pp.158-170, 2012.

I. I. Ivanov, Induction of intestinal Th17 cells by segmented filamentous bacteria, Cell, vol.139, pp.485-498, 2009.

K. Atarashi, Induction of colonic regulatory T cells by indigenous Clostridium species, Science, vol.331, pp.337-341, 2011.

K. Atarashi, Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota, Nature, vol.500, pp.232-236, 2013.

M. Ferrantini, I. Capone, and F. Belardelli, Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use, Biochimie, vol.89, pp.884-893, 2007.

G. M. Lauer and B. D. Walker, Hepatitis C virus infection, N. Engl. J. Med, vol.345, pp.41-52, 2001.

J. H. Noseworthy, Progress report and a farewell, Neurology, vol.73, pp.8-10, 2009.

N. Manel, A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells, Nature, vol.467, pp.214-217, 2010.
URL : https://hal.archives-ouvertes.fr/hal-02193582

N. Servant, EMA-A R package for Easy Microarray data analysis, BMC Res. Notes, vol.3, pp.277-281, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00984710

J. Zhu, H. Yamane, and W. E. Paul, Differentiation of effector CD4 T cell populations (*), Annu Rev Immunol, vol.28, pp.445-489, 2010.

E. A. Ivanova and A. N. Orekhov, T Helper Lymphocyte Subsets and Plasticity in Autoimmunity and Cancer: An Overview, Biomed Res Int, p.327470, 2015.

M. Veldhoen, The role of T helper subsets in autoimmunity and allergy, Curr Opin Immunol, vol.21, pp.606-611, 2009.

B. Golding and D. E. Scott, Vaccine strategies: targeting helper T cell responses, Ann N Y Acad Sci, vol.754, pp.126-137, 1995.

C. Devaud, L. B. John, J. A. Westwood, P. K. Darcy, and M. H. Kershaw, Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy, Oncoimmunology, issue.2, p.25961, 2013.

D. M. Pardoll, The blockade of immune checkpoints in cancer immunotherapy, Nat Rev Cancer, vol.12, pp.252-264, 2012.

M. C. Rissoan, V. Soumelis, N. Kadowaki, G. Grouard, F. Briere et al., Reciprocal control of T helper cell and dendritic cell differentiation, Science, vol.283, pp.1183-1186, 1999.

B. Zygmunt and M. Veldhoen, T helper cell differentiation more than just cytokines, Adv Immunol, vol.109, pp.159-196, 2011.

I. Raphael, S. Nalawade, and T. N. Eagar, Forsthuber TG: T cell subsets and their signature cytokines in autoimmune and inflammatory diseases, Cytokine, vol.74, pp.5-17, 2015.

T. R. Mosmann, H. Cherwinski, M. W. Bond, M. A. Giedlin, and R. L. Coffman, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J Immunol, vol.136, pp.2348-2357, 1986.

M. Touzot, M. Grandclaudon, A. Cappuccio, T. Satoh, C. Martinez-cingolani et al., Combinatorial flexibility of cytokine function during human T helper cell differentiation, Nat Commun, vol.5, p.3987, 2014.

T. Ito, Y. H. Wang, O. Duramad, T. Hori, G. J. Delespesse et al., TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand, J Exp Med, vol.202, pp.1213-1223, 2005.

N. Watanabe, S. Hanabuchi, M. A. Marloie-provost, S. Antonenko, and Y. J. Liu, Soumelis V: Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential, Blood, vol.105, pp.4749-4751, 2005.

E. Volpe, N. Servant, R. Zollinger, S. I. Bogiatzi, P. Hupe et al., Soumelis V: A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses, Nat Immunol, vol.9, pp.650-657, 2008.

N. Manel, D. Unutmaz, and D. R. Littman, The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat, Nat Immunol, vol.9, pp.641-649, 2008.

Y. Chung, S. H. Chang, G. J. Martinez, X. O. Yang, R. Nurieva et al., Critical regulation of early Th17 cell differentiation by interleukin-1 signaling, Immunity, vol.30, pp.576-587, 2009.

L. Zhou, J. E. Lopes, M. M. Chong, I. I. Ivanov, M. R. Victora et al., TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function, Nature, vol.453, pp.236-240, 2008.

A. Naldi, J. Carneiro, C. Chaouiya, and D. Thieffry, Diversity and plasticity of Th cell types predicted from regulatory network modelling, PLoS Comput Biol, vol.6, p.1000912, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00704876

H. D. Kim, T. Shay, O. Shea, E. K. Regev, and A. , Transcriptional regulatory circuits: predicting numbers from alphabets, Science, vol.325, pp.429-432, 2009.

D. Furman and M. M. Davis, New approaches to understanding the immune response to vaccination and infection, Vaccine, vol.33, pp.5271-5281, 2015.

A. Arazi, W. F. Pendergraft, R. M. Ribeiro, A. S. Perelson, and N. Hacohen, Human systems immunology: hypothesis-based modeling and unbiased datadriven approaches, Semin Immunol, vol.25, pp.193-200, 2013.

K. A. Janes, J. G. Albeck, S. Gaudet, P. K. Sorger, D. A. Lauffenburger et al., A systems model of signaling identifies a molecular basis set for cytokineinduced apoptosis, Science, vol.310, pp.1646-1653, 2005.

V. R. Buchholz, M. Flossdorf, I. Hensel, L. Kretschmer, B. Weissbrich et al., Disparate individual fates compose robust CD8+ T cell immunity, vol.340, pp.630-635, 2013.

S. Krishnaswamy, M. H. Spitzer, M. Mingueneau, S. C. Bendall, O. Litvin et al., Systems biology. Conditional density-based analysis of T cell signaling in single-cell data, Science, vol.346, p.1250689, 2014.

A. Zimmer, I. Katzir, E. Dekel, and A. E. Mayo, Alon U: Prediction of multidimensional drug dose responses based on measurements of drug pairs, Proc Natl Acad Sci, vol.113, pp.10442-10447, 2016.

N. Yosef, A. K. Shalek, J. T. Gaublomme, J. H. Lee, Y. Awasthi et al., Dynamic regulatory network controlling TH17 cell differentiation, Nature, vol.496, pp.461-468, 2013.

T. Usui, J. C. Preiss, Y. Kanno, Z. J. Yao, J. H. Bream et al., T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription, J Exp Med, vol.203, pp.755-766, 2006.

N. Schmitt, R. Morita, L. Bourdery, S. E. Bentebibel, S. M. Zurawski et al., Human dendritic cells induce the differentiation of interleukin21-producing T follicular helper-like cells through interleukin-12, Immunity, vol.31, pp.158-169, 2009.

E. Lozano, N. Joller, Y. Cao, V. K. Kuchroo, and D. A. Hafler, The CD226/CD155 interaction regulates the proinflammatory (Th1/Th17)/anti-inflammatory (Th2) balance in humans, J Immunol, vol.191, pp.3673-3680, 2013.

V. Lazarevic, X. Chen, J. H. Shim, E. S. Hwang, E. Jang et al., T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat, Nat Immunol, vol.12, pp.96-104, 2011.

F. Ronchi, C. Basso, S. Preite, A. Reboldi, D. Baumjohann et al., Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1beta production by myeloid cells, Nat Commun, vol.7, p.11541, 2016.

K. Ghoreschi, A. Laurence, X. P. Yang, C. M. Tato, M. J. Mcgeachy et al., Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling, Nature, vol.467, pp.967-971, 2010.

Y. Yang, J. Weiner, Y. Liu, A. J. Smith, D. J. Huss et al., T-bet is essential for encephalitogenicity of both Th1 and Th17 cells, J Exp Med, vol.206, pp.1549-1564, 2009.

W. H. Fridman, F. Pages, C. Sautes-fridman, and J. Galon, The immune contexture in human tumours: impact on clinical outcome, Nat Rev Cancer, vol.12, pp.298-306, 2012.

R. J. Johnston, L. Comps-agrar, J. Hackney, X. Yu, M. Huseni et al., The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function, Cancer Cell, vol.26, pp.923-937, 2014.

J. Larkin, F. S. Hodi, and J. D. Wolchok, Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma, N Engl J Med, vol.373, pp.1270-1271, 2015.

M. Veldhoen, Interleukin 17 is a chief orchestrator of immunity, Nat Immunol, vol.18, pp.612-621, 2017.

C. T. Weaver, R. D. Hatton, P. R. Mangan, and L. E. Harrington, IL-17 family cytokines and the expanding diversity of effector T cell lineages, Annu Rev Immunol, vol.25, pp.821-852, 2007.

S. G. Hymowitz, E. H. Filvaroff, J. P. Yin, J. Lee, L. Cai et al., IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding, EMBO J, vol.20, pp.5332-5341, 2001.

S. Nakae, Y. Komiyama, A. Nambu, K. Sudo, M. Iwase et al., Antigen-specific T cell sensitization is impaired in IL17-deficient mice, causing suppression of allergic cellular and humoral responses, Immunity, vol.17, pp.375-387, 2002.

S. Nakae, A. Nambu, K. Sudo, and Y. Iwakura, Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice, J Immunol, vol.171, pp.6173-6177, 2003.

X. O. Yang, S. H. Chang, H. Park, R. Nurieva, B. Shah et al., Regulation of inflammatory responses by IL-17F, J Exp Med, vol.205, pp.1063-1075, 2008.
DOI : 10.1084/jem.20071978
URL : http://jem.rupress.org/content/205/5/1063.full.pdf

L. A. Tesmer, S. K. Lundy, S. Sarkar, and D. A. Fox, Th17 cells in human disease, Immunol Rev, vol.223, pp.87-113, 2008.

S. Zundler and M. F. Neurath, Interleukin-12: Functional activities and implications for disease, Cytokine Growth Factor Rev, vol.26, pp.559-568, 2015.
DOI : 10.1016/j.cytogfr.2015.07.003

M. , P. , L. Sansonnet, and A. J. Chiquet, VARIABLE SELECTION IN MULTIVARIATE LINEAR MODELS WITH

H. Matrix, , 2017.

M. Perrot-dockès, C. , J. Chiquet, L. Sansonnet, M. Brégère et al., A multivariate variable selection approach for analyzing LC-MS metabolomics data, 2017.

R. Tibshirani, Regression Shrinkage and Selection via the Lasso, Journal of the Royal Statistical Society, p.58, 1996.

N. Meinshausen, Bühlmann P: Stability selection. Series B Statistical Methodology, 2010.

G. Viale, The current state of breast cancer classification, Ann Oncol, vol.23, issue.10, pp.207-217, 2012.

D. Hanahan and R. A. Weinberg, Hallmarks of cancer: the next generation, Cell, vol.144, issue.5, pp.646-74, 2011.

J. Galon, B. Mlecnik, and G. Bindea, Towards the introduction of the 'Immunoscore' in the classification of malignant tumours, J Pathol, vol.232, issue.2, pp.199-209, 2014.

W. H. Fridman, F. Pages, and C. Sautes-fridman, The immune contexture in human tumours: impact on clinical outcome, Nat Rev Cancer, vol.12, issue.4, pp.298-306, 2012.

O. Shea, J. J. Paul, and W. E. , Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells, Science, vol.327, issue.5969, pp.1098-102, 2010.

F. Sallusto, Heterogeneity of Human CD4(+) T Cells Against Microbes, Annu Rev Immunol, vol.34, pp.317-351, 2016.

C. Aspord, A. Pedroza-gonzalez, and M. Gallegos, Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development, J Exp Med, vol.204, issue.5, pp.1037-1084, 2007.

C. Gu-trantien, S. Loi, and S. Garaud, CD4(+) follicular helper T cell infiltration predicts breast cancer survival, J Clin Invest, vol.123, issue.7, pp.2873-92, 2013.

T. Ito, Y. H. Wang, and O. Duramad, TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand, J Exp Med, vol.202, issue.9, pp.1213-1236, 2005.

E. Volpe, N. Servant, and R. Zollinger, A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses, Nat Immunol, vol.9, issue.6, pp.650-657, 2008.

E. Volpe, M. Touzot, and N. Servant, Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production, Blood, vol.114, issue.17, pp.3610-3614, 2009.

C. E. Zielinski, F. Mele, and D. Aschenbrenner, Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta, Nature, vol.484, issue.7395, pp.514-522, 2012.

C. Curtis, S. P. Shah, and S. F. Chin, The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups, Nature, vol.486, issue.7403, pp.346-52, 2012.

H. Matsumoto, A. A. Thike, and H. Li, Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer, Breast Cancer Res Treat, vol.156, issue.2, pp.237-284, 2016.

M. Smid, F. G. Rodriguez-gonzalez, and A. M. Sieuwerts, Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration, Nat Commun, vol.7, p.12910, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01388445

J. Galon, A. Costes, and F. Sanchez-cabo, Type, density, and location of immune cells within human colorectal tumors predict clinical outcome, Science, vol.313, issue.5795, pp.1960-1964, 2006.

S. References-alculumbre and L. Pattarini, Purification of human dendritic cell subsets from peripheral blood, Methods Mol. Biol, vol.1423, issue.2, pp.153-167, 2016.

A. Ballesteros-tato, T. D. Randall, F. E. Lund, R. Spolski, W. J. Leonard et al., T follicular helper cell plasticity shapes pathogenic T helper 2 Cell-mediated immunity to inhaled house dust mite, Immunity, vol.44, pp.259-273, 2016.

N. L. Bernasconi, E. Traggiai, and A. Lanzavecchia, Maintenance of serological memory by polyclonal activation of human memory B cells, Science, vol.298, pp.2199-2202, 2002.

E. B. Brandt and U. Sivaprasad, Th2 Cytokines and atopic dermatitis, J. Clin. Cell. Immunol, vol.2, pp.3-5, 2011.

A. Briot, C. Deraison, M. Lacroix, C. Bonnart, A. Robin et al., Kallikrein 5 induces atopic dermatitislike lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome, J. Exp. Med, vol.206, pp.1135-1147, 2009.

V. L. Bryant, C. S. Ma, D. T. Avery, Y. Li, K. L. Good et al., Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells, J. Immunol, vol.179, pp.8180-8190, 2007.

Y. S. Choi, R. Kageyama, D. Eto, T. C. Escobar, R. J. Johnston et al., ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6, Immunity, vol.34, pp.932-946, 2011.

J. M. Coquet, M. J. Schuijs, M. J. Smyth, K. Deswarte, R. Beyaert et al., Interleukin-21-producing CD4 + T cells promote type 2 immunity to house dust mites, Immunity, vol.43, pp.318-330, 2015.

S. Crotty, T follicular helper cell differentiation, function, and roles in disease, Immunity, vol.41, pp.529-542, 2014.

E. K. Deenick, C. S. Ma, R. Brink, and S. G. Tangye, Regulation of T follicular helper cell formation and function by antigen presenting cells, Curr. Opin. Immunol, vol.23, pp.111-118, 2011.

L. Furio and A. Hovnanian, Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy, Biol. Chem, vol.395, pp.945-958, 2014.

P. R. Giacomin, M. C. Siracusa, K. P. Walsh, R. K. Grencis, M. Kubo et al., Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection, J. Immunol, vol.189, pp.4371-4378, 2012.

G. Zaretsky, A. , J. J. Taylor, I. L. King, F. A. Marshall et al., T follicular helper cells differentiate from Th2 cells in response to helminth antigens, J. Exp. Med, vol.206, pp.991-999, 2009.

H. J. Gould, B. J. Sutton, A. J. Beavil, R. L. Beavil, N. Mccloskey et al., The biology of IGE and the basis of on, 2003.

, allergic disease, Annu. Rev. Immunol, vol.214, issue.5, pp.579-628

M. Grewe, C. A. Bruijnzeel-koomen, E. Schöpf, T. Thepen, A. G. Langeveldwildschut et al., A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis, Immunol. Today, vol.19, pp.1285-1292, 1998.

S. I. Gringhuis, T. M. Kaptein, B. A. Wevers, M. Van-der-vlist, E. J. Klaver et al., Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production, Nat. Commun, vol.5, p.5074, 2014.

K. Hatzi, J. P. Nance, M. A. Kroenke, M. Bothwell, E. K. Haddad et al., BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms, J. Exp. Med, vol.212, pp.539-553, 2015.

J. He, L. M. Tsai, Y. A. Leong, X. Hu, C. S. Ma et al., Circulating precursor CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure, Immunity, vol.39, pp.770-781, 2013.

A. Hovnanian, Netherton syndrome: skin inflammation and allergy by loss of protease inhibition, Cell Tissue Res, vol.351, pp.289-300, 2013.

T. Ito, Y. H. Wang, O. Duramad, T. Hori, G. J. Delespesse et al., TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand, J. Exp. Med, vol.202, pp.1213-1223, 2005.

T. Ito, M. Yang, Y. H. Wang, R. Lande, J. Gregorio et al., Plasmacytoid dendritic cells prime IL-10producing T regulatory cells by inducible costimulator ligand, J. Exp. Med, vol.204, pp.105-115, 2007.

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, Immunity, vol.42, pp.1159-1170, 2015.

D. M. Kemeny, The role of the T follicular helper cells in allergic disease, Cell. Mol. Immunol, vol.9, pp.386-389, 2012.

C. H. Kim, H. W. Lim, J. R. Kim, L. Rott, P. Hillsamer et al., Unique gene expression program of human germinal center T helper cells, Blood, vol.104, pp.1952-1960, 2004.

M. A. Kroenke, D. Eto, M. Locci, M. Cho, T. Davidson et al., Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation, J. Immunol, vol.188, pp.3734-3744, 2012.

S. Kusam, L. M. Toney, H. Sato, and A. L. Dent, Inhibition of Th2 differentiation and GATA-3 expression by BCL-6, J. Immunol, vol.170, pp.2435-2441, 2003.

J. M. Leyva-castillo, P. Hener, P. Michea, H. Karasuyama, S. Chan et al., Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade, Nat. Commun, vol.4, p.2847, 2013.

H. E. Liang, R. L. Reinhardt, J. K. Bando, B. M. Sullivan, I. C. Ho et al., Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity, Nat. Immunol, vol.13, pp.58-66, 2011.

Y. J. Liu, V. Soumelis, N. Watanabe, T. Ito, Y. H. Wang et al., TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation, 2007.

, Annu. Rev. Immunol, vol.25, pp.193-219

M. Locci, C. Havenar-daughton, E. Landais, J. Wu, M. A. Kroenke et al., Human circulating PD-1 + CXCR3 ? CXCR5 + memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses, Immunity, vol.39, pp.758-769, 2013.

A. Lonati, S. Licenziati, A. D. Canaris, S. Fiorentini, G. Pasolini et al., Reduced production of both Th1 and Tc1 lymphocyte subsets in atopic dermatitis (AD), Clin. Exp. Immunol, vol.115, pp.1-5, 1999.

C. S. Ma and E. K. Deenick, Human T follicular helper (Tfh) cells and disease, Immunol. Cell Biol, vol.92, pp.64-71, 2014.

C. S. Ma, D. T. Avery, A. Chan, M. Batten, J. Bustamante et al., Functional STAT3 deficiency compromises the generation of human T follicular helper cells, Blood, vol.119, pp.3997-4008, 2012.

R. Morita, N. Schmitt, S. E. Bentebibel, R. Ranganathan, L. Bourdery et al., Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion, Immunity, vol.34, pp.108-121, 2011.

M. Nakazawa, N. Sugi, H. Kawaguchi, N. Ishii, H. Nakajima et al., Predominance of type 2 cytokine-producing CD4+ and CD8+ cells in patients with atopic dermatitis, J. Allergy Clin. Immunol, vol.99, pp.70030-70037, 1997.

J. H. Nies, C. Bär, G. Schlenvoigt, B. Fahlbusch, G. Zwacka et al., IL-4 supplemented B-cell cultures of allergic children show reduced IgA and IgG production in response to additional stimulation with IL-10, J. Investig. Allergol. Clin. Immunol, vol.12, pp.99-106, 2002.

J. Niu, Z. Song, X. Yang, Z. Zhai, H. Zhong et al., Increased circulating follicular helper T cells and activated B cells correlate with disease severity in patients with psoriasis, J. Eur. Acad. Dermatol. Venereol, vol.29, pp.1791-1796, 2015.

O. Shea, J. J. , and W. E. Paul, Mechanisms underlying lineage commitment and plasticity of helper CD4 + T cells, Science, vol.327, pp.1098-1102, 2010.

J. Pène, F. Rousset, F. Brière, I. Chrétien, X. Paliard et al., IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma, J. Immunol, vol.141, pp.1218-1224, 1988.

T. R. Ramalingam, J. T. Pesce, M. M. Mentink-kane, S. Madala, A. W. Cheever et al., Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin, 2009.

, J. Immunol, vol.182, pp.6452-6459

N. Schmitt, R. Morita, L. Bourdery, S. E. Bentebibel, S. M. Zurawski et al., Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12, Immunity, vol.31, pp.158-169, 2009.

N. Schmitt, J. Bustamante, L. Bourdery, S. E. Bentebibel, S. Boisson-dupuis et al., IL-12 receptor ?1 deficiency alters in vivo T follicular helper cell response in humans, Blood, vol.121, pp.3375-3385, 2013.

N. Schmitt, Y. Liu, S. E. Bentebibel, I. Munagala, L. Bourdery et al., The cytokine TGF-? co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells, Nat. Immunol, vol.15, pp.856-865, 2014.

J. U. Shin, S. H. Kim, H. Kim, J. Y. Noh, S. Jin et al., TSLP is a potential initiator of collagen synthesis, 2016.

, J. Invest. Dermatol, vol.136, pp.507-515

V. Soumelis, P. A. Reche, H. Kanzler, W. Yuan, G. Edward et al., Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP, Nat. Immunol, vol.3, pp.673-680, 2002.

S. G. Tangye, C. S. Ma, R. Brink, and E. K. Deenick, The good, the bad and the ugly-TFH cells in human health and disease, Nat. Rev. Immunol, vol.13, pp.412-426, 2013.

G. Trinchieri, Interleukin-12 and the regulation of innate resistance and adaptive immunity, Nat. Rev. Immunol, vol.3, pp.133-146, 2003.

H. Ueno, J. Banchereau, and C. G. Vinuesa, Pathophysiology of T follicular helper cells in humans and mice, Nat. Immunol, vol.16, pp.142-152, 2015.

G. A. Van-roey, M. A. Arias, J. S. Tregoning, G. Rowe, and R. J. Shattock, Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice, Eur. J. Immunol, vol.42, pp.353-363, 2012.

E. Volpe, N. Servant, R. Zollinger, S. I. Bogiatzi, P. Hupé et al., A critical function for transforming growth factorbeta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses, Nat. Immunol, vol.9, pp.650-657, 2008.

E. Volpe, L. Pattarini, C. Martinez-cingolani, S. Meller, M. H. Donnadieu et al., Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis, J. Allergy Clin. Immunol, vol.134, pp.373-381, 2014.

Y. H. Wang, T. Ito, Y. H. Wang, B. Homey, N. Watanabe et al., Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells, Immunity, vol.24, pp.827-838, 2006.

J. S. Weinstein, K. Lezon-geyda, Y. Maksimova, S. Craft, Y. Zhang et al., Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes, Blood, vol.124, pp.3719-3729, 2014.

S. Ying, B. O'connor, J. Ratoff, Q. Meng, K. Mallett et al., Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity, J. Immunol, vol.174, pp.8183-8190, 2005.

I. Yusuf, R. Kageyama, L. Monticelli, R. J. Johnston, D. Ditoro et al., Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150), J. Immunol, vol.185, pp.190-202, 2010.

S. F. Ziegler and D. Artis, Sensing the outside world: TSLP regulates barrier immunity, Nat. Immunol, vol.11, pp.289-293, 2010.

W. Abou-jaoudé, D. A. Ouattara, and M. Kaufman, From structure to dynamics: frequency tuning in the p53-Mdm2 network I. Logical approach, J. Theor. Biol, vol.258, pp.561-577, 2009.

R. Albert, J. J. Collins, and L. Glass, Introduction to focus issue: quantitative approaches to genetic networks, Chaos, vol.23, p.25001, 2013.

Y. E. Antebi, S. Reich-zeliger, Y. Hart, A. Mayo, I. Eizenberg et al., Mapping differentiation under mixed culture conditions reveals a tunable continuum of T cell fates, PLoS Biol, vol.11, 2013.

G. Arellano, J. Argil, E. Azpeitia, M. Benítez, M. Carrillo et al., Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis, BMC Bioinformatics, vol.12, p.490, 2011.

G. Batt, D. Ropers, H. De-jong, J. Geiselmann, R. Mateescu et al., Validation of qualitative models of genetic regulatory networks by model checking: analysis of the nutritional stress response in Escherichia coli, Bioinformatics, vol.21, pp.19-28, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00171939

D. Bérenguier, C. Chaouiya, P. T. Monteiro, A. Naldi, E. Remy et al., Dynamical modeling and analysis of large cellular regulatory networks, Chaos, vol.23, p.25114, 2013.

C. Berge, The Theory of Graphs, 2001.

N. Bonzanni, A. Garg, A. Feenstra, J. Schutte, S. Kinston et al., Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model, Bioinformatics, vol.13, pp.80-88, 2013.

S. Bornholdt, L. Brim, M. Ce?ka, and D. ?afránek, Boolean network models of cellular regulation: prospects and limitations, Formal Methods for Dynamical Systems, vol.5, pp.63-112, 2008.

N. Chabrier and F. Fages, Symbolic model checking of biochemical networks, Computational Methods in Systems Biology, vol.2602, pp.149-162, 2003.

C. Chaouiya, A. Naldi, and D. Thieffry, Logical modelling of gene regulatory networks with GINsim, Bacterial Molecular Networks, vol.804, pp.463-479, 2012.

C. Chaouiya, E. Remy, B. Mossé, and D. Thieffry, Qualitative analysis of regulatory graphs: a computational tool based on a discrete formal framework, Positive Systems, vol.294, pp.119-126, 2003.

A. Cimatti, E. Clarke, E. Giunchiglia, F. Giunchiglia, M. Pistore et al., NuSMV2: an opensource tool for symbolic model checking, Computer Aided Verification, vol.2404, pp.359-364, 2002.

E. Clarke, O. Grumberg, P. , and D. , Model Checking, 1999.

J. Comet, M. Noual, A. Richard, J. Aracena, L. Calzone et al., On circuit functionality in Boolean networks, Bull. Math. Biol, vol.75, pp.906-919, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01242396

H. De-jong, Modeling and simulation of genetic regulatory systems: a literature review, J. Comput. Biol, vol.9, pp.67-103, 2002.

V. Devloo, P. Hansen, and M. Labbé, Identification of all steady states in large networks by logical analysis, Bull. Math. Biol, vol.65, pp.61-63, 2003.
URL : https://hal.archives-ouvertes.fr/hal-01255591

E. Dubrova and M. Teslenko, A SAT-based algorithm for finding attractors in synchronous Boolean networks, IEEE/ACM Trans. Comput. Biol. Bioinform, vol.8, pp.1393-1399, 2011.

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.

A. Fauré, A. Naldi, C. Chaouiya, and D. Thieffry, Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle, Bioinformatics, vol.22, pp.124-131, 2006.

H. Garavel, R. Mateescu, F. Lang, and W. Serwe, CADP 2006: a toolbox for the construction and analysis of distributed processes, Computer Aided Verification, vol.4590, pp.158-163, 2007.
URL : https://hal.archives-ouvertes.fr/inria-00189021

A. Garg, A. Di-cara, I. Xenarios, L. Mendoza, D. Micheli et al., Synchronous versus asynchronous modeling of gene regulatory networks, Bioinformatics, vol.24, pp.1917-1925, 2008.

K. Ghoreschi, A. Laurence, X. P. Yang, C. M. Tato, M. J. Mcgeachy et al., Generation of pathogenic TH17 cells in the absence of TGF-? signalling, Nature, vol.467, pp.967-971, 2010.

L. Grieco, L. Calzone, I. Bernard-pierrot, F. Radvanyi, B. Kahn-perlès et al., Integrative modelling of the influence of MAPK network on cancer cell fate decision, PLoS Comput. Biol, vol.9, p.21003286, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-02152259

A. Hegazy, M. Peine, C. Helmstetter, I. Panse, A. Fröhlich et al., Interferons direct Th2 cell reprogramming to generate a stable GATA3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions, Immunity, vol.32, pp.116-128, 2010.

T. Kam, T. Villa, R. K. Brayton, and A. L. Sangiovanni-vincentelli, Multivalued decision diagrams: theory and applications, Multiple-Valued Logic, vol.4, pp.9-62, 1998.

G. Karlebach and R. Shamir, Modelling and analysis of gene regulatory networks, Nat. Rev. Mol. Cell Biol, vol.9, pp.770-780, 2008.

D. Kozen, Results on the propositional µ-calculus, Theor. Comp. Sci, vol.27, pp.90125-90131, 1983.

Y. K. Lee, H. Turner, C. L. Maynard, J. R. Oliver, D. Chen et al., Late developmental plasticity in the T helper 17 lineage, Immunity, vol.30, pp.92-107, 2009.

A. Lomuscio, C. Pecheur, R. , and F. , Automatic verification of knowledge and time with NuSMV, International Joint Conference on Artificial Intelligence, pp.1384-1389, 2007.

P. Martinez-sosa and L. Mendoza, The regulatory network that controls the differentiation of t lymphocytes, Biosystems, vol.2, pp.96-103, 2013.

R. Mateescu, P. T. Monteiro, E. Dumas, and H. Jong, CTRL: extension of CTL with regular expressions and fairness operators to verify genetic regulatory networks, Theor. Comp. Sci, vol.412, pp.2854-2883, 2011.
URL : https://hal.archives-ouvertes.fr/inria-00610831

L. Mendoza, A network model for the control of the differentiation process in Th cells, Biosystems, vol.84, pp.101-114, 2006.

L. Mendoza and F. Pardo, A robust model to describe the differentiation of T-helper cells, Theory Biosci, vol.129, pp.283-293, 2010.

L. Mendoza, X. , and I. , A method for the generation of standardized qualitative dynamical systems of regulatory networks, Theor. Biol. Med. Model, vol.3, p.13, 2006.

P. T. Monteiro, C. , and C. , Efficient verification for logical models of regulatory networks, of Advances in Intelligent and Soft Computing, vol.154, pp.259-267, 2012.

, Frontiers in Bioengineering and Biotechnology | Bioinformatics and Computational Biology, vol.2, p.12, 2015.

. Abou-jaoudé, Model checking revealing T-cell plasticity

T. R. Mosmann, H. Cherwinski, M. W. Bond, M. A. Giedlin, and R. L. Coffman, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol, vol.136, pp.2348-2357, 1986.

T. R. Mosmann and R. L. Coffman, TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties, Annu. Rev. Immunol, vol.7, pp.145-173, 1989.

K. M. Murphy and S. L. Reiner, The lineage decisions of helper T cells, Nat. Rev. Immunol, vol.2, pp.933-944, 2002.

S. Nakayamada, H. Takahashi, Y. Kanno, and J. J. Shea, Helper T cell diversity and plasticity, Curr. Opin. Immunol, vol.24, pp.297-302, 2012.

A. Naldi, J. Carneiro, C. Chaouiya, and D. Thieffry, Diversity and plasticity of Th cell types predicted from regulatory network modelling, PLoS Comput. Biol, vol.6, p.1000912, 2010.
DOI : 10.1371/journal.pcbi.1000912
URL : https://hal.archives-ouvertes.fr/inserm-00704876

A. Naldi, P. T. Monteiro, C. , and C. , Efficient handling of large signalling-regulatory networks by focusing on their core control, Computational Methods in Systems Biology, vol.7605, pp.288-306, 2012.

A. Naldi, P. T. Monteiro, C. Mussel, H. A. Kestler, D. Thieffry et al., Cooperative development of logical modelling standards and tools with CoLoMoTo, 2014.
DOI : 10.1093/bioinformatics/btv013
URL : https://academic.oup.com/bioinformatics/article-pdf/31/7/1154/438964/btv013.pdf

A. Naldi, E. Remy, D. Thieffry, C. , and C. , Dynamically consistent reduction of logical regulatory graphs, Theor. Comp. Sci, vol.412, pp.2207-2218, 2011.
DOI : 10.1016/j.tcs.2010.10.021
URL : https://hal.archives-ouvertes.fr/hal-01284743

A. Naldi, D. Thieffry, C. , and C. , Decision diagrams for the representation and analysis of logical models of genetic networks, Computational Methods in Systems Biology, vol.4695, pp.233-247, 2007.

O. Shea, J. , P. , and W. , Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells, Science, vol.327, pp.1098-1102, 2010.

M. Peine, S. Rausch, C. Helmstetter, A. Fröhlich, A. Hegazy et al., , 2013.

T. Stable and . Th1, Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation, PLoS Biol, vol.11, p.1001633

E. Remy, R. , and P. , From minimal signed circuits to the dynamics of Boolean regulatory networks, Bioinformatics, vol.24, pp.220-226, 2008.
URL : https://hal.archives-ouvertes.fr/hal-01306956

A. Saadatpour, R. Albert, and T. Reluga, A reduction method for Boolean network models proven to conserve attractors, SIAM J. Appl. Dyn. Syst, vol.12, 1997.

J. Saez-rodriguez, L. Simeoni, J. A. Lindquist, R. Hemenway, U. Bommhardt et al., A logical model provides insights into T cell receptor signaling, PLoS Comput. Biol, vol.3, p.163, 2007.

R. Samaga and S. Klamt, Modeling approaches for qualitative and semiquantitative analysis of cellular signaling networks, Cell Commun. Signal, vol.11, p.43, 2013.

M. Schwarick and M. Heiner, CSL model checking of biochemical networks with interval decision diagrams, Computational Methods in Systems Biology, vol.5688, pp.296-312, 2009.

H. Siebert and A. Bockmayr, Incorporating time delays into the logical analysis of gene regulatory networks, Computational Methods in Systems Biology, vol.4210, pp.169-183, 2006.

G. Stoll, E. Viara, E. Barillot, C. , and L. , Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm, BMC Syst. Biol, vol.6, p.116, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00762304

D. Thieffry, Dynamical roles of biological regulatory circuits, Brief. Bioinformatics, vol.8, pp.220-225, 2007.

R. Thomas, R. Ari, H. J. Van-den-ham, R. J. De-boer, H. J. Van-den-ham et al., From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation, Immunol. Cell Biol, vol.20, pp.860-868, 1990.

A. Veliz-cuba, A. S. Jarrah, and R. Laubenbacher, Polynomial algebra of discrete models in systems biology, Bioinformatics, vol.26, pp.1637-1643, 2010.

R. Wang, A. Saadatpour, A. , and R. , Boolean modeling in systems biology: an overview of methodology and applications, Phys. Biol, vol.9, p.55001, 2012.

D. M. Wittmann, J. Krumsiek, J. Saez-rodriguez, D. A. Lauffenburger, S. Klamt et al., Transforming Boolean models to continuous models: methodology and application to T-cell receptor signaling, BMC Syst. Biol, vol.3, p.98, 2009.

A. Xie and P. A. Beerel, Efficient state classification of finite-state Markov chains, IEEE Trans. Comput. Aided Des. Integrated Circ. Syst, vol.17, pp.1334-1339, 1998.

X. O. Yang, R. Nurieva, G. J. Martinez, H. S. Kang, Y. Chung et al., Molecular antagonism and plasticity of regulatory and inflammatory T cell programs, Immunity, vol.29, pp.44-56, 2008.

J. G. Zañudo, A. , and R. , An effective network reduction approach to find the dynamical repertoire of discrete dynamic networks, Chaos, vol.23, p.25111, 2013.

, Conflict of Interest Statement: The authors declare that the research was conducted

J. Banchereau, F. Briere, C. Caux, J. Davoust, S. Lebecque et al., Immunobiology of Dendritic Cells. AnnuRevImmunol, pp.767-811, 2000.

P. Guermonprez, J. Valladeau, L. Zitvogel, C. Théry, and S. Amigorena, Antigen presentation and T cell stimulation by dendritic cells, Annu Rev Immunol, vol.20, pp.621-67, 2002.

N. Valeyev, C. Hundhausen, Y. Umezawa, N. Kotov, G. Williams et al., A systems model for immune cell interactions unravels the mechanism of inflammation in human skin, PLoS Comput Biol, vol.6, 2010.

M. F. Neurath, Cytokines in inflammatory bowel disease, Nat Rev Immunol. Nature Publishing Group, vol.14, pp.329-371, 2014.

. Shen-orr-s, Towards A Cytokine-Cell Interaction Knowledgebase Of The Adaptive Immune System, Pac Symp Biocomput, pp.1-10, 2009.

Z. Frankenstein, U. Alon, and I. R. Cohen, The immune-body cytokine network defines a social architecture of cell interactions, Biol Direct, vol.1, p.32, 2006.

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

K. W. Moore, R. Malefyt, L. Robert, and A. O. Garra,

, Receptor. AnnuRevImmunol, vol.1, pp.683-765, 2001.

Q. Huang, D. Liu, P. Majewski, L. C. Schulte, J. M. Korn et al., The plasticity of dendritic cell responses to pathogens and their components, Science, vol.294, pp.870-875, 2001.

C. Buelens, F. Willems, G. Piérard, J. P. Delville, and T. Velu, Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells, Eur J Immunol, vol.25, pp.2668-72, 1995.

C. Wu, C. Orozco, J. Boyer, M. Leglise, J. Goodale et al., BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources, Genome Biol, vol.10, p.130, 2009.

J. K. Baillie, H. Brown, and T. C. Freeman, Hume D a. An expression atlas of human primary cells: inference of gene function from coexpression networks, BMC Genomics. BMC Genomics, vol.14, p.632, 2013.

F. W. Goetz, J. Planas, and S. Mackenzie, Tumor necrosis factors, Dev Comp Immunol, vol.28, p.23, 2004.

J. M. Pitt, E. Stavropoulos, P. S. Redford, A. M. Beebe, G. J. Bancroft et al., Blockade of IL-10 signaling during bacillus Calmette-Guérin vaccination enhances and sustains Th1, Th17, and innate lymphoid IFN-? and IL-17 responses and increases protection to Mycobacterium tuberculosis infection, J Immunol, vol.189, pp.4079-87, 2012.

E. Zigmond, B. Bernshtein, G. Friedlander, C. R. Walker, S. Yona et al., Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis, Immunity, vol.40, pp.720-753, 2014.

C. M. Wilke, L. Wang, S. Wei, I. Kryczek, E. Huang et al., Endogenous interleukin10 constrains Th17 cells in patients with inflammatory bowel disease, J Transl Med. BioMed Central Ltd, vol.9, p.217, 2011.

M. Stassen, E. Schmitt, and T. Bopp, From interleukin-9 to T helper 9 cells, Ann N Y Acad Sci, vol.1247, pp.56-68, 2012.

K. E. Graeber and N. J. Olsen, Th17 cell cytokine secretion profile in host defense and autoimmunity, Inflamm Res, vol.61, pp.87-96, 2012.

L. Tortola, E. Rosenwald, B. Abel, H. Blumberg, M. Schäfer et al., Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk, J Clin Invest, vol.122, 2012.

C. Shimura, T. Satoh, K. Igawa, K. Aritake, Y. Urade et al., Dendritic cells express hematopoietic prostaglandin D synthase and function as a source of prostaglandin D2 in the skin, Am J Pathol, vol.176, pp.227-264, 2010.

K. Hirota, H. Yoshitomi, M. Hashimoto, S. Maeda, S. Teradaira et al., Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model, J Exp Med, vol.204, pp.2803-2815, 2007.

M. Kramer, B. M. Schulte, D. Eleveld-trancikova, M. Van-hout-kuijer, L. Toonen et al., Cross-talk between human dendritic cell subsets influences expression of RNA sensors and inhibits picornavirus infection, J Innate Immun, vol.2, pp.360-70, 2010.

D. Piccioli, C. Sammicheli, S. Tavarini, S. Nuti, E. Frigimelica et al., Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation, Immunobiology, vol.113, pp.4232-4239, 2009.

Y. Lou, C. Liu, G. J. Kim, Y. Liu, P. Hwu et al., Plasmacytoid Dendritic Cells Synergize with Myeloid Dendritic Cells in the Induction of Antigen-Specific Antitumor Immune Responses, J Immunol, vol.178, p.24, 2007.

S. Schuster, B. Hurrell, and F. Tacchini-cottier, Crosstalk between neutrophils and dendritic cells: a context-dependent process, J Leukoc Biol, vol.94, pp.671-676, 2013.

I. S. Ludwig, T. Geijtenbeek, and Y. Van-kooyk, Two way communication between neutrophils and dendritic cells, Curr Opin Pharmacol, vol.6, pp.408-421, 2006.

J. Jiao, A. Dragomir, P. Kocabayoglu, A. H. Rahman, A. Chow et al., Central role of conventional dendritic cells in regulation of bone marrow release and survival of neutrophils, J Immunol, vol.192, pp.3374-82, 2014.

C. Hivroz, K. Chemin, M. Tourret, and A. Bohineust, Crosstalk between T Lymphocytes and Dendritic Cells, Crit Rev Immunol, vol.32, pp.139-155, 2012.

. Cooper, A. Fuchs, and M. Colonna, Caligiuri M a. NK cell and DC interactions, Trends Immunol, vol.25, pp.47-52, 2004.

E. Scotet, S. Nedellec, M. Devilder, S. Allain, and M. Bonneville, Bridging innate and adaptive immunity through ?? T-dendritic cell crosstalk, Front Biosci, pp.6872-6885, 2008.
DOI : 10.2741/3195

D. C. Kirouac, C. Ito, E. Csaszar, A. Roch, M. Yu et al., Dynamic interaction networks in a hierarchically organized tissue, Mol Syst Biol. Nature Publishing Group, vol.6, p.417, 2010.

P. S. Podobed, F. J. Alibhai, C. Chow, and M. , Identification of Cardiac Clock-Controlled Genes Using Open Access Bioinformatics Data, Circadian Regulation of Myocardial Sarcomeric Titin-cap, vol.9, p.104907, 2014.

A. Romeu and L. Arola, Classical dynamin DNM1 and DNM3 genes attain maximum expression in the normal human central nervous system, BMC Res Notes, vol.7, p.188, 2014.

B. Ingalls, Mathematical Modeling in Systems Biology: An Introduction, pp.1-396, 2013.

B. F. Sallusto and A. Lanzavecchia, Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha, J Exp Med, p.179, 1994.

J. M. Trevejo, M. W. Marino, N. Philpott, R. Josien, E. C. Richards et al., TNFalpha-dependent maturation of local dendritic cells is critical for activating the 25 25 adaptive immune response to virus infection, Proc Natl Acad Sci U S A, vol.98, pp.12162-12169, 2001.

J. F. Arrighi, M. Rebsamen, F. Rousset, V. Kindler, and C. Hauser, A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers, J Immunol, vol.166, pp.3837-3882, 2001.

Y. Yamaguchi, H. Tsumura, M. Miwa, and K. Inaba, Contrasting effects of TGF-beta 1 and TNF-alpha on the development of dendritic cells from progenitors in mouse bone marrow, Stem Cells, vol.15, pp.144-153, 1997.

D. 'andrea-a,-aste-amezaga, M. Valiante, N. M. Ma, X. Kubin, M. Trinchieri et al., Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells, J Exp Med, vol.178, pp.1041-1049, 1993.

A. Liberzon, A. Subramanian, R. Pinchback, H. Thorvaldsdóttir, P. Tamayo et al., Molecular signatures database (MSigDB) 3.0, Bioinformatics, vol.27, pp.1739-1779, 2011.

Q. Li, N. J. Birkbak, B. Gyorffy, Z. Szallasi, and A. C. Eklund, Jetset: selecting the optimal microarray probe set to represent a gene, BMC Bioinformatics. BioMed Central Ltd, vol.12, p.474, 2011.

R. Article, P. , G. , and A. Myelopoiesis, Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-b

C. Martínez-cingolani, , 2004.

, Institut National de la SantéSant´Santé et de la Recherche M ´ edicale U932, vol.2

, Electron microscopy established the presence of Birbeck granules, an intracellular organelle specific to LCs. LC differentiation was not observed from tonsil BDCA-1 1 and BDCA-3 1 subsets. TSLP 1 TGF-b LCs had a mature phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent CD4 1 T-helper (Th) cell expansion and differentiation into Th2 cells with increased production of tumor necrosis factor-a and interleukin-6 compared with CD34-derived LCs. Our findings establish a novel LC differentiation pathway from BDCA-1 1 blood DCs with potential implications in epithelial inflammation. Therapeutic targeting of TSLP may interfere with tissue LC repopulation from circulating precursors, The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a keratinocytederived cytokine involved in epithelial inflammation, cooperates with transforming growth factor (TGF)-b for the generation of LCs. We show that primary human blood BDCA-1 1 , but not BDCA-3 1 , dendritic cells (DCs) stimulated with TSLP and TGF-b harbor a typical CD1a 1 Langerin 1 LC phenotype, vol.124, p.2411, 2014.

, 24 were used when indicated. Peripheral blood CD34 1 cells were cultured for 9 to 10 days in Yssel medium supplemented with 10% heat inactivated fetal calf serum, penicillinstreptomycin, 50 ng/mL GM-CSF (Miltenyi), 100 ng/mL Fms-like tyrosin kinase 3 (Flt3) ligand (R&D Systems), and 10 ng/mL TNF-a (R&D Systems). Culture media and cytokines were refreshed on day 5 of culture, and 10 ng/mL of TGF-calf serum, U/mL (Prepotech) and prostaglandin E2 at 1 mg/mL (Sigma-Aldrich), as a Jonuleit cocktail

G. Ng/ml, 100 ng/mL IL-4 (Miltenyi), and 10 ng/mL density gradient centrifugation (FicollPaque GE Healthcare), enrichment (CD4 T cell Isolation kit

, After 6 days of coculture, T cells were counted, reseeded at 1 3 10 6 /mL in flatbottom 96-well plates, and restimulated for 24 hours with anti-CD3/CD28 microbeads (Dynal). Cell culture supernatants were collected, and cytokine measurement was performed by multiplex bead assay, Miltenyi Biotec), and further FACS sorting purification. Purity was .98%

, Millipore) on a Bio-Plex-200 reader (Biorad)

J. Seneschal, R. A. Clark, A. Gehad, C. M. Baecher-allan, and T. S. Kupper, Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells, Immunity, vol.36, issue.5, pp.873-884, 2012.

E. Klechevsky, R. Morita, and M. Liu, Functional specializations of human epidermal Langerhans cells and CD141 dermal dendritic cells, Immunity, vol.29, issue.3, pp.497-510, 2008.

H. Moll, H. Fuchs, C. Blank, R. ¨-ollinghoff, and M. , Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells, Eur J Immunol, vol.23, issue.7, pp.1595-1601, 1993.

F. Geissmann, M. C. Dieu-nosjean, and C. Dezutter, Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin, J Exp Med, vol.196, issue.4, pp.417-430, 2002.

J. Ashworth and R. M. Mackie, A quantitative analysis of the Langerhans cell in chronic plaque psoriasis, Clin Exp Dermatol, vol.11, issue.6, pp.594-599, 1986.

M. Merad, M. G. Manz, and H. Karsunky, Langerhans cells renew in the skin throughout life under steady-state conditions, Nat Immunol, vol.3, issue.12, pp.1135-1141, 2002.

L. Chorro, A. Sarde, and M. Li, Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network, J Exp Med, vol.206, issue.13, pp.3089-3100, 2009.

F. Ginhoux, F. Tacke, and V. Angeli, Langerhans cells arise from monocytes in vivo, Nat Immunol, vol.7, issue.3, pp.265-273, 2006.

Y. Wang, K. J. Szretter, and W. Vermi, IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia, Nat Immunol, vol.13, issue.8, pp.753-760, 2012.

M. Greter, I. Lelios, and P. Pelczar, Stromaderived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia, Immunity, vol.37, issue.6, pp.1050-1060, 2012.

D. H. Kaplan, M. O. Li, M. C. Jenison, W. D. Shlomchik, R. A. Flavell et al., Autocrine/paracrine TGFbeta1 is required for the development of epidermal Langerhans cells, J Exp Med, vol.204, issue.11, pp.2545-2552, 2007.

T. A. Borkowski, J. J. Letterio, A. G. Farr, and M. C. Udey, A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells, J Exp Med, vol.184, issue.6, pp.2417-2422, 1996.

S. I. Katz, K. Tamaki, and D. H. Sachs, Epidermal Langerhans cells are derived from cells originating in bone marrow, Nature, vol.282, issue.5736, pp.324-326, 1979.

B. Volc-platzer, G. Stingl, K. Wolff, W. Hinterberg, and W. Schnedl, Cytogenetic identification of allogeneic epidermal Langerhans cells in a bonemarrow-graft recipient, N Engl J Med, vol.310, issue.17, pp.1123-1124, 1984.

C. Caux, C. Dezutter-dambuyant, D. Schmitt, and J. Banchereau, GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells, Nature, vol.360, issue.6401, pp.258-261, 1992.

F. Geissmann, C. Prost, J. P. Monnet, M. Dy, N. Brousse et al., Transforming growth factor beta1, in the presence of granulocyte/ macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells, J Exp Med, vol.187, issue.6, pp.961-966, 1998.

T. Ito, M. Inaba, and K. Inaba, A CD1a1/CD11c1 subset of human blood dendritic cells is a direct precursor of Langerhans cells, J Immunol, vol.163, issue.3, pp.1409-1419, 1999.

J. Kanitakis, E. Morelon, P. Petruzzo, L. Badet, and J. M. Dubernard, Self-renewal capacity of human BLOOD, vol.124, 2014.

A. Dzionek, A. Fuchs, and P. Schmidt, BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood, J Immunol, vol.165, issue.11, pp.6037-6046, 2000.

V. Soumelis, P. A. Reche, and H. Kanzler, Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP, Nat Immunol, vol.3, issue.7, pp.673-680, 2002.

P. A. Reche, V. Soumelis, and D. M. Gorman, Human thymic stromal lymphopoietin preferentially stimulates myeloid cells, J Immunol, vol.167, issue.1, pp.336-343, 2001.

K. Arima, N. Watanabe, S. Hanabuchi, M. Chang, S. C. Sun et al., Distinct signal codes generate dendritic cell functional plasticity, Sci Signal, vol.3, issue.105, p.4, 2010.

Y. J. Liu, V. Soumelis, and N. Watanabe, TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation, Annu Rev Immunol, vol.25, pp.193-219, 2007.

H. Jonuleit, K. ¨-uhn, U. , M. ¨-uller, and G. , Proinflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions

, Eur J Immunol, vol.27, issue.12, pp.3135-3142, 1997.

F. Husson, J. Josse, L. ?-e-s, and M. J. Factominer, Multivariate Exploratory Data Analysis and Data Mining with R. R package version 1, vol.16, 2011.

S. J. Santegoets, S. Gibbs, and K. Kroeze, Transcriptional profiling of human skin-resident Langerhans cells and CD1a1 dermal dendritic cells: differential activation states suggest distinct functions, J Leukoc Biol, vol.84, issue.1, pp.143-151, 2008.

H. Strobl, C. Bello-fernandez, and E. Riedl, flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows singlecell dendritic cell cluster formation under serumfree conditions, Blood, vol.90, issue.4, pp.1425-1434, 1997.

M. S. Birbeck, An electron microscopy study of basal melanocytes and high level clear cells (Langerhans cells) in vitiligo, J Invest Dermatol, vol.37, pp.51-64, 1961.

M. Thépautth´thépaut, J. Valladeau, and A. Nurisso, Structural studies of langerin and Birbeck granule: a macromolecular organization model, Biochemistry, vol.48, issue.12, pp.2684-2698, 2009.

E. Segura, M. Touzot, and A. Bohineust, Human inflammatory dendritic cells induce Th17 cell differentiation, Immunity, vol.38, issue.2, pp.336-348, 2013.

A. Tang, M. Amagai, L. G. Granger, J. R. Stanley, and M. C. Udey, Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin, Nature, vol.361, issue.6407, pp.82-85, 1993.

K. Ouwehand, S. J. Santegoets, D. P. Bruynzeel, R. J. Scheper, T. D. De-gruijl et al., CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis, Eur J Immunol, vol.38, issue.11, pp.3050-3059, 2008.

E. J. Villablanca and J. R. Mora, A two-step model for Langerhans cell migration to skin-draining LN

, Eur J Immunol, vol.38, issue.11, pp.2975-2980, 2008.

M. Collin, V. Bigley, M. Haniffa, and S. Hambleton, Human dendritic cell deficiency: the missing ID?, Nat Rev Immunol, vol.11, issue.9, pp.575-583, 2011.

K. Liu, G. D. Victora, and T. A. Schwickert, In vivo analysis of dendritic cell development and homeostasis, Science, vol.324, issue.5925, pp.392-397, 2009.

M. Merad, P. Sathe, J. Helft, J. Miller, and A. Mortha, The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting, Annu Rev Immunol, vol.31, pp.563-604, 2013.

H. Strobl, E. Riedl, and C. Scheinecker, TGF-beta 1 dependent generation of LAG1 dendritic cells from CD341 progenitors in serum-free medium, Adv Exp Med Biol, vol.417, pp.161-165, 1997.

D. Strunk, K. Rappersberger, and C. Egger, Generation of human dendritic cells/Langerhans cells from circulating CD341 hematopoietic progenitor cells, Blood, vol.87, issue.4, pp.1292-1302, 1996.

K. Palucka, J. Banchereau, and I. Mellman, Designing vaccines based on biology of human dendritic cell subsets, Immunity, vol.33, issue.4, pp.464-478, 2010.

E. Segura, J. Valladeau-guilemond, M. H. Donnadieu, X. Sastre-garau, V. Soumelis et al., Characterization of resident and migratory dendritic cells in human lymph nodes, J Exp Med, vol.209, issue.4, pp.653-660, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00723792

V. Bigley, M. Haniffa, and S. Doulatov, The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency, J Exp Med, vol.208, issue.2, pp.227-234, 2011.

M. Chopin and S. L. Nutt, Establishing and maintaining the Langerhans cell network

, Semin Cell Dev Biol

H. Ema, T. Suda, Y. Miura, and H. Nakauchi, Colony formation of clone-sorted human hematopoietic progenitors, Blood, vol.75, issue.10, pp.1941-1946, 1990.

M. Merad, P. Hoffmann, and E. Ranheim, Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease, Nat Med, vol.10, issue.5, pp.510-517, 2004.

S. Ebner, V. A. Nguyen, and M. Forstner, Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells, J Allergy Clin Immunol, vol.119, issue.4, pp.982-990, 2007.

S. Nakajima, B. Z. Igyarto, and T. Honda, Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling, J Allergy Clin Immunol, vol.129, issue.4, pp.1048-1055, 2012.

M. Veldhoen, C. Uyttenhove, and J. Van-snick, Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset, Nat Immunol, vol.9, issue.12, pp.1341-1346, 2008.

W. Yao, Y. Zhang, and R. Jabeen, Interleukin-9 is required for allergic airway inflammation mediated by the cytokine TSLP, Immunity, vol.38, issue.2, 2013.

T. Vicsek, The bigger picture, Nature, vol.418, issue.6894, p.131, 2002.

G. Nicolis and C. Nicolis, Foundations of Complex Systems, European Review, vol.17, issue.02, p.237, 2009.

Z. N. Oltvai and A. L. Barabasi, Life's complexity pyramid, Science, vol.298, issue.5594, pp.763-764, 2002.

F. Mazzocchi, Exceeding the limits of reductionism and determinism using complexity theory, EMBO reports, vol.9, issue.1, pp.10-14, 2008.

B. Edmonds, Syntactic Measures of Complexity, 1999.

D. Gatherer, So what do we really mean when we say that systems biology is holistic?, BMC systems biology, vol.4, p.22, 2010.

H. Kitano, Systems biology: a brief overview, Science, vol.295, issue.5560, pp.1662-1664, 2002.

H. Ge, A. J. Walhout, and M. Vidal, Integrating 'omic' information: a bridge between genomics and systems biology, Trends in genetics : TIG, vol.19, issue.10, pp.551-560, 2003.

F. S. Collins, M. Morgan, and A. Patrinos, The Human Genome Project: lessons from largescale biology, Science, vol.300, issue.5617, pp.286-290, 2003.

M. P. Stumpf, Estimating the size of the human interactome, Proceedings of the National Academy of Sciences of the United States of America, vol.105, pp.6959-6964, 2008.

M. L. Blinov, J. R. Faeder, B. Goldstein, and W. S. Hlavacek, A network model of early events in epidermal growth factor receptor signaling that accounts for combinatorial complexity, Bio Systems, vol.83, issue.2-3, pp.136-151, 2006.

W. S. Hlavacek, J. R. Faeder, M. L. Blinov, A. S. Perelson, and B. Goldstein, The complexity of complexes in signal transduction, Biotechnology and bioengineering, vol.84, issue.7, pp.783-794, 2003.

R. Linding, Multivariate signal integration, Nature reviews. Molecular cell biology, vol.11, issue.6, p.391, 2010.

V. Soumelis, L. Pattarini, P. Michea, and A. Cappuccio, Systems approaches to unravel innate immune cell diversity, environmental plasticity and functional specialization, Current opinion in immunology, vol.32, pp.42-47, 2015.

K. A. Janes, A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis, Science, vol.310, issue.5754, pp.1646-1653, 2005.

A. Cappuccio, Combinatorial code governing cellular responses to complex stimuli, Nature communications, vol.6, p.6847, 2015.

J. Jia, Mechanisms of drug combinations: interaction and network perspectives, Nature reviews. Drug discovery, vol.8, issue.2, pp.111-128, 2009.

T. Bollenbach and R. Kishony, Resolution of gene regulatory conflicts caused by combinations of antibiotics, Molecular cell, vol.42, issue.4, pp.413-425, 2011.

K. W. Gong, Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells, Genome biology, vol.8, issue.7, p.149, 2007.

M. Natarajan, K. M. Lin, R. C. Hsueh, and P. C. Sternweis, A global analysis of cross-talk in a mammalian cellular signalling network, Nature cell biology, vol.8, issue.6, pp.571-580, 2006.

R. Medzhitov, Recognition of microorganisms and activation of the immune response, Nature, vol.449, issue.7164, pp.819-826, 2007.

J. Zhu, H. Yamane, and W. E. Paul, Differentiation of effector CD4 T cell populations (*), Annual review of immunology, vol.28, pp.445-489, 2010.

M. C. Rissoan, Reciprocal control of T helper cell and dendritic cell differentiation, Science, vol.283, issue.5405, pp.1183-1186, 1999.

K. Murphy, Janeway's Immunobiology (Garland Science), 2012.

, Dendritic cells in a mature age, Nature reviews. Immunology, vol.6, issue.6, pp.476-483, 2006.

M. L. Kapsenberg, Dendritic-cell control of pathogen-driven T-cell polarization, Nature reviews. Immunology, vol.3, issue.12, pp.984-993, 2003.

X. Tao, S. Constant, P. Jorritsma, and K. Bottomly, Strength of TCR signal determines the costimulatory requirements for Th1 and Th2 CD4+ T cell differentiation, Journal of immunology, vol.159, issue.12, pp.5956-5963, 1997.

C. Ruedl, M. F. Bachmann, and M. Kopf, The antigen dose determines T helper subset development by regulation of CD40 ligand, European journal of immunology, vol.30, issue.7, pp.2056-2064, 2000.

M. F. Mackey, Dendritic cells require maturation via CD40 to generate protective antitumor immunity, Journal of immunology, vol.161, issue.5, pp.2094-2098, 1998.

H. Tanaka, C. E. Demeure, M. Rubio, G. Delespesse, and M. Sarfati, Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (Th2) or Th1/Th2 effectors. Role of stimulator/responder ratio, The Journal of experimental medicine, vol.192, issue.3, pp.405-412, 2000.

J. R. Groom, CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation, Immunity, vol.37, issue.6, pp.1091-1103, 2012.

B. Zygmunt and M. Veldhoen, T helper cell differentiation more than just cytokines, Advances in immunology, vol.109, pp.159-196, 2011.

C. S. Hsieh, Development of TH1 CD4+ T cells through IL-12 produced by Listeriainduced macrophages, Science, vol.260, issue.5107, pp.547-549, 1993.

R. Banchereau, Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines, Nature communications, vol.5, p.5283, 2014.

N. Manel, D. Unutmaz, and D. R. Littman, The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat, Nature immunology, vol.9, issue.6, pp.641-649, 2008.

E. Volpe, A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses, Nature immunology, vol.9, issue.6, pp.650-657, 2008.

T. Ito, TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand, The Journal of experimental medicine, vol.202, issue.9, pp.1213-1223, 2005.

N. Schmitt, The cytokine TGF-beta co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells, Nature immunology, vol.15, issue.9, pp.856-865, 2014.

T. R. Mosmann, H. Cherwinski, M. W. Bond, M. A. Giedlin, and R. L. Coffman, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, Journal of immunology, vol.136, issue.7, pp.2348-2357, 1986.

T. R. Mosmann and R. L. Coffman, TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties, Annual review of immunology, vol.7, pp.145-173, 1989.

E. Rouvier, M. F. Luciani, M. G. Mattei, F. Denizot, and P. Golstein, CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene, Journal of immunology, vol.150, issue.12, pp.5445-5456, 1993.

L. Steinman, A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage, Nature medicine, vol.13, issue.2, pp.139-145, 2007.

S. Eyerich, Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling, The Journal of clinical investigation, vol.119, issue.12, pp.3573-3585, 2009.

V. Dardalhon, IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells, Nature immunology, vol.9, issue.12, pp.1347-1355, 2008.

R. Morita, Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion, Immunity, vol.34, issue.1, pp.108-121, 2011.

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.

C. E. Zielinski, Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta, Nature, vol.484, issue.7395, pp.514-518, 2012.

Y. H. Wang, A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma, The Journal of experimental medicine, vol.207, issue.11, pp.2479-2491, 2010.

Y. Endo, Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3, Immunity, vol.35, issue.5, pp.733-745, 2011.

G. Beriou, TGF-beta induces IL-9 production from human Th17 cells, Journal of immunology, vol.185, issue.1, pp.46-54, 2010.

M. T. Wong, A High-Dimensional Atlas of Human T Cell Diversity Reveals TissueSpecific Trafficking and Cytokine Signatures, Immunity, vol.45, issue.2, pp.442-456, 2016.

M. Yamamura, Defining protective responses to pathogens: cytokine profiles in leprosy lesions, Science, vol.254, issue.5029, pp.277-279, 1991.

D. S. Robinson, Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma, The New England journal of medicine, vol.326, issue.5, pp.298-304, 1992.

A. M. Bentley, Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. The American review of respiratory disease, vol.146, pp.500-506, 1992.

T. Nakayama, Th2 Cells in Health and Disease, Annual review of immunology, vol.35, pp.53-84, 2017.

H. Chang and K. C. Nadeau, IL-4Ralpha Inhibitor for Atopic Disease, Cell, vol.170, issue.2, p.222, 2017.

A. E. Lovett-racke, Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes, Immunity, vol.21, issue.5, pp.719-731, 2004.

S. Sriram, D. Solomon, R. V. Rouse, and L. Steinman, Identification of T cell subsets and B lymphocytes in mouse brain experimental allergic encephalitis lesions, Journal of immunology, vol.129, issue.4, pp.1649-1651, 1982.

M. K. Racke, Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease, The Journal of experimental medicine, vol.180, issue.5, pp.1961-1966, 1994.

M. K. Racke, Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course, Journal of immunology, vol.154, issue.1, pp.450-458, 1995.

Y. Cao, Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis, Science translational medicine, vol.7, issue.287, pp.287-274, 2015.

S. K. Bedoya, B. Lam, K. Lau, and J. Larkin, Th17 cells in immunity and autoimmunity, p.986789, 2013.

Z. J. Liu, P. K. Yadav, J. L. Su, J. S. Wang, and K. Fei, Potential role of Th17 cells in the pathogenesis of inflammatory bowel disease, World journal of gastroenterology, vol.15, pp.5784-5788, 2009.

E. Volpe, L. Battistini, and G. Borsellino, Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis, Mediators of inflammation, p.475158, 2015.

L. Cosmi, F. Liotta, M. E. Romagnani, S. Annunziato, and F. , Th17 cells: new players in asthma pathogenesis, Allergy, vol.66, issue.8, pp.989-998, 2011.

J. Zhao, C. M. Lloyd, and A. Noble, Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling, Mucosal immunology, vol.6, issue.2, pp.335-346, 2013.

A. Cavani, D. Pennino, and K. Eyerich, Th17 and Th22 in skin allergy, Chemical immunology and allergy, vol.96, pp.39-44, 2012.

L. Zhang, Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis, PloS one, vol.7, issue.4, p.31000, 2012.

R. Zhao, Elevated peripheral frequencies of Th22 cells: a novel potent participant in obesity and type 2 diabetes, PloS one, vol.9, issue.1, 2014.

X. Xu, Increased Th22 cells are independently associated with Th17 cells in type 1 diabetes, Endocrine, vol.46, issue.1, pp.90-98, 2014.

S. Cheuk, Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis, Journal of immunology, vol.192, issue.7, pp.3111-3120, 2014.

X. Y. Yang, Th22, but not Th17 might be a good index to predict the tissue involvement of systemic lupus erythematosus, Journal of clinical immunology, vol.33, issue.4, pp.767-774, 2013.

D. A. Randolph and C. G. Fathman, Cd4+Cd25+ regulatory T cells and their therapeutic potential, Annual review of medicine, vol.57, pp.381-402, 2006.

E. M. Ling, Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease, Lancet, vol.363, issue.9409, pp.608-615, 2004.

C. Baecher-allan and D. A. Hafler, Human regulatory T cells and their role in autoimmune disease, Immunological reviews, vol.212, pp.203-216, 2006.

C. P. Jones, L. G. Gregory, B. Causton, G. A. Campbell, and C. M. Lloyd, Activin A and TGF-beta promote T(H)9 cell-mediated pulmonary allergic pathology, The Journal of allergy and clinical immunology, vol.129, issue.4, pp.1000-1010, 2012.

M. H. Kaplan, M. M. Hufford, and M. R. Olson, The development and in vivo function of T helper 9 cells, Nature reviews. Immunology, vol.15, issue.5, pp.295-307, 2015.

C. Schlapbach, Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity, Science translational medicine, vol.6, issue.219, pp.219-218, 2014.

N. Simpson, Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus, Arthritis and rheumatism, vol.62, issue.1, pp.234-244, 2010.

R. Christensen and J. , Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17-and activated B-cells and correlates with progression, PloS one, vol.8, issue.3, p.57820, 2013.

H. J. Park, Insights into the role of follicular helper T cells in autoimmunity, Immune network, vol.14, issue.1, pp.21-29, 2014.

K. Szabo, Expansion of circulating follicular T helper cells associates with disease severity in childhood atopic dermatitis, 2017.

R. Kamekura, Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma, Clinical immunology, vol.158, issue.2, pp.204-211, 2015.

F. Mbeunkui and D. J. Johann, Cancer and the tumor microenvironment: a review of an essential relationship, Cancer chemotherapy and pharmacology, vol.63, issue.4, pp.571-582, 2009.

G. Trinchieri, Cancer and inflammation: an old intuition with rapidly evolving new concepts, Annual review of immunology, vol.30, pp.677-706, 2012.

J. Galon, Type, density, and location of immune cells within human colorectal tumors predict clinical outcome, Science, vol.313, issue.5795, pp.1960-1964, 2006.

C. Miracco, Utility of tumour-infiltrating CD25+FOXP3+ regulatory T cell evaluation in predicting local recurrence in vertical growth phase cutaneous melanoma, Oncology reports, vol.18, issue.5, pp.1115-1122, 2007.

D. Mougiakakos, Intratumoral forkhead box P3-positive regulatory T cells predict poor survival in cyclooxygenase-2-positive uveal melanoma, Cancer, vol.116, issue.9, pp.2224-2233, 2010.

G. J. Bates, Quantification of regulatory T cells enables the identification of highrisk breast cancer patients and those at risk of late relapse, Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol.24, issue.34, pp.5373-5380, 2006.

M. Gobert, Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome, Cancer research, vol.69, issue.5, pp.2000-2009, 2009.

C. Badoual, Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers, Cancer Research, vol.12, issue.2, pp.465-472, 2006.

D. M. Frey, High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients, International journal of cancer, vol.126, issue.11, pp.2635-2643, 2010.

M. Tosolini, Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer, Cancer research, vol.71, issue.4, pp.1263-1271, 2011.

W. H. Fridman, F. Pages, C. Sautes-fridman, and J. Galon, The immune contexture in human tumours: impact on clinical outcome, Nature reviews. Cancer, vol.12, issue.4, pp.298-306, 2012.

X. Dai, Breast cancer intrinsic subtype classification, clinical use and future trends, American journal of cancer research, vol.5, issue.10, pp.2929-2943, 2015.

B. D. Lehmann, Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies, The Journal of clinical investigation, vol.121, issue.7, pp.2750-2767, 2011.

C. Aspord, Breast cancer instructs dendritic cells to prime interleukin 13secreting CD4+ T cells that facilitate tumor development, The Journal of experimental medicine, vol.204, issue.5, pp.1037-1047, 2007.

C. Gu-trantien, CD4(+) follicular helper T cell infiltration predicts breast cancer survival, The Journal of clinical investigation, vol.123, issue.7, pp.2873-2892, 2013.
DOI : 10.1172/jci67428
URL : http://www.jci.org/articles/view/67428/files/pdf

G. Plitas, Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer. Immunity, vol.45, issue.5, pp.1122-1134, 2016.

L. Mobius-w-&-laan, Physical and Mathematical Modeling in Experimental Papers, Cell, vol.163, issue.7, pp.1577-1583, 2015.

S. Motta and F. Pappalardo, Mathematical modeling of biological systems, Briefings in bioinformatics, vol.14, issue.4, pp.411-422, 2013.

N. Torres and G. Santos, The (Mathematical) Modeling Process in Biosciences, Frontiers in genetics, vol.6, p.354, 2015.

C. Chassagnole, N. Noisommit-rizzi, J. W. Schmid, K. Mauch, and M. Reuss, Dynamic modeling of the central carbon metabolism of Escherichia coli, Biotechnology and bioengineering, vol.79, issue.1, pp.53-73, 2002.

J. J. Tyson, K. C. Chen, and B. Novak, Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell, Current opinion in cell biology, vol.15, issue.2, pp.221-231, 2003.

M. Rizzi, M. Baltes, T. U. Reuss, and M. , In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II. Mathematical model, Biotechnology and bioengineering, vol.55, issue.4, pp.592-608, 1997.

S. Kauffman, Homeostasis and differentiation in random genetic control networks, Nature, vol.224, issue.5215, pp.177-178, 1969.

J. Saez-rodriguez, A logical model provides insights into T cell receptor signaling, PLoS computational biology, vol.3, issue.8, p.163, 2007.

S. Gupta, S. S. Bisht, R. Kukreti, S. Jain, and S. K. Brahmachari, Boolean network analysis of a neurotransmitter signaling pathway, Journal of theoretical biology, vol.244, issue.3, pp.463-469, 2007.

A. Naldi, J. Carneiro, C. Chaouiya, and D. Thieffry, Diversity and plasticity of Th cell types predicted from regulatory network modelling, PLoS computational biology, vol.6, issue.9, p.1000912, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00704876

D. Furman and M. M. Davis, New approaches to understanding the immune response to vaccination and infection, Vaccine, vol.33, issue.40, pp.5271-5281, 2015.

J. Gomez-rodriguez, Differential expression of interleukin-17A and-17F is coupled to T cell receptor signaling via inducible T cell kinase, Immunity, vol.31, issue.4, pp.587-597, 2009.

H. Bonsang-kitzis, Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis, Oncoimmunology, vol.5, issue.1, p.1061176, 2016.

B. Ruffell, Leukocyte composition of human breast cancer, Proceedings of the National Academy of Sciences of the United States of America, vol.109, issue.8, pp.2796-2801, 2012.

R. D. Hatton, TGF-beta in Th17 cell development: the truth is out there, Immunity, vol.34, issue.3, pp.288-290, 2011.

T. Ito, Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand, The Journal of experimental medicine, vol.204, issue.1, pp.105-115, 2007.

C. Jacquemin, OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response, Immunity, vol.42, issue.6, pp.1159-1170, 2015.

A. Arazi, W. F. Pendergraft, R. M. Ribeiro, A. S. Perelson, and N. Hacohen, Human systems immunology: hypothesis-based modeling and unbiased data-driven approaches, Seminars in immunology, vol.25, issue.3, pp.193-200, 2013.
DOI : 10.1016/j.smim.2012.11.003
URL : http://europepmc.org/articles/pmc3836867?pdf=render

W. J. Chae, The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 CellMediated Inflammation, Immunity, vol.44, issue.2, pp.246-258, 2016.

A. Slovick, Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms, The Journal of allergy and clinical immunology, vol.139, issue.6, pp.1830-1839, 2017.
DOI : 10.1016/j.jaci.2016.09.024
URL : http://www.jacionline.org/article/S0091674916311861/pdf

N. W. Palm, Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity, Immunity, vol.39, issue.5, pp.976-985, 2013.

R. Zhao, HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 Tcell function, Proceedings of the National Academy of Sciences of the United States of America, vol.110, issue.24, pp.9879-9884, 2013.

K. Yomogida, Y. K. Chou, and C. Q. Chu, Superantigens induce IL-17 production from polarized Th1 clones, Cytokine, vol.63, issue.1, pp.6-9, 2013.
DOI : 10.1016/j.cyto.2013.04.015
URL : http://europepmc.org/articles/pmc3683377?pdf=render

J. M. Marchingo, T cell signaling. Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion, Science, vol.346, issue.6213, pp.1123-1127, 2014.

E. Volpe, Thymic stromal lymphopoietin links keratinocytes and dendritic cellderived IL-23 in patients with psoriasis, The Journal of allergy and clinical immunology, vol.134, issue.2, pp.373-381, 2014.

F. Mosconi, T. J. , N. Desprat, D. K. Sinha, J. Allemand et al., Some nonlinear challenges in biology, Nonlinearity, vol.21, issue.8, 2008.

D. M. Pardoll, The blockade of immune checkpoints in cancer immunotherapy, Nature reviews. Cancer, vol.12, issue.4, pp.252-264, 2012.

L. Chen and X. Han, Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future, The Journal of clinical investigation, vol.125, issue.9, pp.3384-3391, 2015.

P. A. Ott, F. S. Hodi, H. L. Kaufman, J. M. Wigginton, and J. D. Wolchok, Combination immunotherapy: a road map, Journal for immunotherapy of cancer, vol.5, p.16, 2017.
DOI : 10.1186/s40425-017-0218-5
URL : https://jitc.biomedcentral.com/track/pdf/10.1186/s40425-017-0218-5

R. J. Johnston, The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function, Cancer cell, vol.26, issue.6, pp.923-937, 2014.
DOI : 10.1016/j.ccell.2014.10.018
URL : https://doi.org/10.1016/j.ccell.2014.10.018

J. Larkin, F. S. Hodi, and J. D. Wolchok, Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma, The New England journal of medicine, vol.373, issue.13, pp.1270-1271, 2015.
DOI : 10.1056/nejmoa1504030
URL : https://cronfa.swan.ac.uk/Record/cronfa25005/Download/0025005-20072017114154.pdf

A. D. Weston and L. Hood, Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine, Journal of proteome research, vol.3, issue.2, pp.179-196, 2004.