2 research outputs found
IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells
Interleukinâ1 (ILâ1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which ILâ1 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 ILâ1 receptor type 1 (ILâ1R1)âdependent ILâ1β expression by myeloid cells in the draining lymph nodes. This myeloidâderived ILâ1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GMâCSF (+) Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GMâCSFâproducing Th17 cells led to ameliorated disease in mice deficient for ILâ1R1 specifically in T cells. Importantly, pathogenicity of ILâ1R1âdeficient T cells was fully restored by ILâ23 polarization and expansion in vitro. Therefore, our data demonstrate that ILâ1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation