| First Author | Scherlinger M | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 600 | PubMed ID | 34193612 |
| Mgi Jnum | J:330070 | Mgi Id | MGI:6728697 |
| Doi | 10.1126/scitranslmed.abi4994 | Citation | Scherlinger M, et al. (2021) Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis. Sci Transl Med 13(600) |
| abstractText | Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor-beta axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin-dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue. |
