Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting gamma delta T (gamma delta T-17) cells and Th17 cells. However, T cells from Il17a(-/-) mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1 beta, and IL-23. Furthermore, treatment with IL-1 beta or IL-17A at induction of EAE restores disease in Il17a(-/-) mice. Importantly, mobilization of IL-1 beta-producing neutrophils and inflammatory monocytes and activation of gamma delta T17 cells is reduced in Il17a(-/-) mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1 beta-secreting myeloid cells that prime pathogenic gamma delta T17 and Th17 cells.