IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells

EMBO J. 2017 Jan 4;36(1):102-115. doi: 10.15252/embj.201694615. Epub 2016 Nov 8.

Abstract

Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL-1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL-1 receptor type 1 (IL-1R1)-dependent IL-1β expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM-CSF+ Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GM-CSF-producing Th17 cells led to ameliorated disease in mice deficient for IL-1R1 specifically in T cells. Importantly, pathogenicity of IL-1R1-deficient T cells was fully restored by IL-23 polarization and expansion in vitro Therefore, our data demonstrate that IL-1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation.

Keywords: EAE; GM‐CSF; IL‐1; Th17; autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis*
  • Interleukin-1 / metabolism*
  • Mice
  • Pertussis Toxin / administration & dosage
  • Pertussis Toxin / toxicity
  • Th17 Cells / chemistry*
  • Th17 Cells / physiology*

Substances

  • Interleukin-1
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Pertussis Toxin