A Direct Link between IL-17 and Regulatory T cells in Autoimmune Colitis

Abstract

Abstract Inflammatory bowel diseases are rising in prevalence globally. While current treatments aim to achieve remission, there remains no cure for this disease. IL-17 family cytokines are important players in inflammation, but clinical trials using anti-IL-17A or IL-17RA blocking antibodies have failed for Crohn’s disease, due to exacerbated inflammation in some patients. While anti-IL-17 antibodies have shown efficacy in the treatment of other autoimmune diseases like psoriasis, patients can often develop Crohn’s disease as a side effect of these drugs. These data suggest a protective role of IL-17 in gut inflammation. The proper activation and function of regulatory T cells is essential for the protection against intestinal autoimmune inflammation. Using the naïve T cell transfer model of colitis in mice, we found that IL-17RA-null iTregs, transferred after the establishment of colitis, were less effective at controlling the colitis compared to WT iTregs. Naïve T cells cultured ex vivo in iTreg polarizing conditions had an increase in complete iTreg differentiation when stimulated with IL-17 cytokines. Our results indicate that IL-17 directly signals to Tregs and assists their anti-inflammatory role during autoimmune gut inflammation. Although the underlying mechanism remains under study, this finding suggests an inhibitory loop between IL-17 and Tregs for the control of overt inflammation.