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.
Induction of autoimmune neuroinflammation requires expansion of self‐antigen‐specific CD4 T cells in an IL‐1‐dependent manner, which can be substituted by IL‐23 stimulation.
Pertussis toxin promotes IL‐1β expression by myeloid cells.
Th17 cells express higher levels of IL‐1R1 compared to other CD4 T cells.
IL‐1 signaling results in the expansion of autoreactive Th17 cells.
IL‐23 can substitute the lack of IL‐1 signaling in CD4 T cells.
- Received April 21, 2016.
- Revision received September 5, 2016.
- Accepted September 22, 2016.
- © 2016 The Authors
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