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.e6. doi: 10.1016/j.immuni.2020.01.002. Epub 2020 Feb 4.


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.

Keywords: IL-17; IL-1β; Th17 cells; autoimmunity; experimental autoimmune encephalomyelitis; inflammatory monocyte; multiple sclerosis; neutrophil; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Autoimmunity / genetics
  • Autoimmunity / immunology*
  • Central Nervous System / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / deficiency
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism*
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Intraepithelial Lymphocytes / immunology*
  • Intraepithelial Lymphocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism


  • Autoantigens
  • IL1B protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23