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

McGinley, Aoife MSutton, Caroline EEdwards, Sarah CLeane, Charlotte MDeCourcey, JosephTeijeiro, AnaHamilton, John ABoon, LouisDjouder, NabilMills, Kingston H G2024-02-082024-02-082020-02-18Immunity . 2020;52(2):342-356http://hdl.handle.net/20.500.12105/17561Interleukin-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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsAutoantigensAutoimmunityCentral Nervous SystemEncephalomyelitis, Autoimmune, ExperimentalInterleukin-17Interleukin-1betaInterleukin-23Intraepithelial LymphocytesMiceMice, Inbred C57BLMice, KnockoutMonocytesMyeloid CellsNeutrophilsTh17 CellsInterleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells.Attribution-NonCommercial-NoDerivatives 4.0 Internacional3202349052234210.1016/j.immuni.2020.01.0021097-4180Immunityopen access