Essential role of IL-17A in Tregs induction in autoimmune uveitis

Abstract The signature cytokine of Th17 cells, IL-17A, is a pro-inflammatory cytokine associated with various autoimmune diseases in patients and in animal models. However, clinical trials targeting IL-17A in autoimmune disease have been disappointing. We found that Foxp3+ T regulatory cells (Tregs), express both IL17A receptor subunits, i.e. IL17RA and IL17RC., We therefore hypothesized that IL-17A may regulate the induction and/or function of Tregs. Recombinant IL-17A significantly increased the in-vitro polarization of T cells into Tregs. We next investigated the number of Tregs in WT and IL-17A−/− mice that were immunized for experimental autoimmune uveitis. Although there was no significant difference in Treg frequency between WT and IL-17A−/− mice before disease onset, IL-17A− /− mice failed to induce Tregs as efficiently as WT mice when disease progressed. Interestingly, IL-17A−/− mice developed similar disease severity when compared to WT mice, which may in part be due to an impairment in Treg induction. Our data suggest that IL-17A is involved in Tregs induction and/or maintenance, and that this has a role in controlling the (auto)immune response.