T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis.

ABSTRACT: Interleukin 1? (IL-1?) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1? during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1? production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1?, whereas ATP stimulation triggered T cell production of IL-1? via ASC-NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1?. Together these data reveal a critical role for IL-1? produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system.

SUBMITTER: Martin BN 

PROVIDER: S-EPMC5385929 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature