Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells
Citation:
McGinley AM, Sutton CE, Edwards SC, Leane CM, DeCourcey J, Teijeiro A, Hamilton JA, Boon L, Djouder N, Mills KHG. Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells. Immunity. 2020 Feb 18;52(2):342-356.e6Download Item:
Abstract:
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.
Sponsor
Grant Number
Science Foundation Ireland
11/PI/ 1036
Author's Homepage:
http://people.tcd.ie/millsk
Author: Mills, Kingston
Type of material:
Journal ArticleCollections
Series/Report no:
Immunity;52;
2;
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Full text availableKeywords:
vitroculture, Interleukin-17A (IL-17A), autoimmune diseases, IL-17, IL-1β, Th17 cells, Autoimmunity, Experimental autoimmune encephalomyelitis, Inflammatory monocyte, Multiple sclerosis, γδ T cells, NeutrophilDOI:
http://dx.doi.org/10.1016/j.immuni.2020.01.002Metadata
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