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

Mufazalov, IA;Schelmbauer, C;Regen, T;Kuschmann, J;Wanke, F;Gabriel, LA;Hauptmann, J;Mller, W;Pinteaux, E;Kurschus, FC;Waisman, A;

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-1 expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1 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.