Essential role of IL-17A in activating Treg cells in autoimmune uveitis

Abstract

Abstract The balance between Th17 cells and regulatory T (Treg) cells is critical for host homeostasis. The signature cytokine of Th17 cells, IL-17A, is a pro-inflammatory cytokine associated with various autoimmune diseases in patients and in animal models. Our previous study demonstrated that IL-17A limits pathogenicity of Th17 cells by inducing IL-24. In this study, we investigate the role of IL-17A in regulating Treg cells. In-vitro studies showed that IL-17A promotes both the differentiation and suppressive functions of Treg cells. Adoptive transfer of IL-17A-treated Treg cells is more potent to ameliorate experimental autoimmune uveitis (EAU) in mice when compared to the control Treg cells. We found that the induction of Treg cells is impaired in Il17ra −/−mice after EAU immunization and Il17ra −/−naïve T cells are less effective in their differentiation into Treg cells in EAU compared to wild-type cells. Mechanistic studies revealed that IL-17A activates NF-kB signaling and inhibits TAZ, a Foxp3 suppressor, during Treg cell differentiation. In conclusion, our data suggest that IL-17A is involved in Tregs induction and/or maintenance, and that this has a role in controlling the autoimmune response. Natural Science Foundation of Guangdong Province (2019A1515010956, 2021A1515010569, 2022A1515012450) Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center.