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 γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a−/− mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. Furthermore, treatment with IL-1β or IL-17A at induction of EAE restores disease in Il17a−/− mice. Importantly, mobilization of IL-1β-producing neutrophils and inflammatory monocytes and activation of γδT17 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-1β-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells. [Display omitted] •IL-17A is required for priming but not effector function of Th17 cells in EAE•IL-17A-defective mice are highly resistant to induction of EAE—rescued by IL-1β•IL-17A acts in a positive feedback loop to induce IL-1β production early in EAE•IL-17A-induced chemokines mobilize IL-1β-secreting neutrophils and monocytes Experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, is an autoimmune disease in which the cytokine IL-17A is thought to mediate CNS tissue damage. McGinley et al. report a new role for IL-17A in mobilizing innate immune cells that secrete IL-1β, an inflammatory cytokine that primes encephalitogenic T cells.