Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, defect in the regulatory T (T reg ) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted cells via P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction PSGL-1 blocked suppressive properties particularly follicular triggering Syk phosphorylation an increase intracytosolic calcium. Mechanistically, P-selectin engagement on induced down-regulation transforming growth factor–? axis, altering phenotype limiting their immunosuppressive responses. SLE, found up-regulation P- E-selectin both microparticles soluble forms correlated activity. Last, blocking mouse model improved cardinal features disease, such as anti-dsDNA antibody concentrations kidney pathology. Overall, our results identify P-selectin–dependent pathway validate it potential therapeutic avenue.