| First Author | Mufazalov IA | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 1 | Pages | 102-115 |
| PubMed ID | 27827809 | Mgi Jnum | J:239106 |
| Mgi Id | MGI:5824950 | Doi | 10.15252/embj.201694615 |
| Citation | Mufazalov IA, et al. (2017) IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells. EMBO J 36(1):102-115 |
| abstractText | 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-1beta expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1beta 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. |
