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

• DOI: 10.15252/embj.201694615
• Publication Date: 2016-11-09T11:09:49Z
• Authors: Ilgiz A Mufazalov; Carsten Schelmbauer; Tommy Regen; Janina Kuschmann; Florian Wanke; Laureen A Gabriel; Judith Hauptmann; Werner Müller; Emmanuel Pinteaux; Florian C Kurschus; Ari Waisman
• Keywords: Columbia university

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.