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Les sélectines inhibent la fonction des lymphocytes T régulateurs et contribuent à la pathogénie du lupus érythémateux systémique

Abstract : Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, an interferon signature, and a defect in the T regulatory cells (Tregs) compartment. In this work, we identified that platelets from active SLE patients preferentially interacted with Tregs via the P-selectin/PSGL-1 axis. Selectin interaction with PSGL-1 blocked the regulatory/suppressive properties of Tregs and follicular Tregs by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Tregs induced a downregulation of the TGF-beta axis, altering Tregs phenotype and limiting their immunosuppressive response. In patients, we found a significant upregulation of P- and E-selectin levels both expressed by microparticles and in their soluble forms that correlated with SLE disease activity. Finally, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease. Overall, our results identify a selectin-dependent pathway active in SLE patients and validate it as a potential therapeutic avenue.
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Submitted on : Tuesday, October 13, 2020 - 11:28:11 AM
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Marc Scherlinger. Les sélectines inhibent la fonction des lymphocytes T régulateurs et contribuent à la pathogénie du lupus érythémateux systémique. Médecine humaine et pathologie. Université de Bordeaux, 2020. Français. ⟨NNT : 2020BORD0100⟩. ⟨tel-02965390⟩

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