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T cell–intrinsic ASC critically promotes TH17-mediated experimental autoimmune encephalomyelitis
- Source :
- Nature Immunology; May 2016, Vol. 17 Issue: 5 p583-592, 10p
- Publication Year :
- 2016
-
Abstract
- Interleukin 1β (IL-1β) is critical for the in vivo survival, expansion and effector function of IL-17–producing helper T (TH17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1β during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell–intrinsic inflammasome that drives IL-1β production during TH17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1β, whereas ATP stimulation triggered T cell production of IL-1β via ASC-NLRP3–dependent caspase-8 activation. IL-1R was detected on TH17 cells but not on type 1 helper T (TH1) cells, and ATP-treated TH17 cells showed enhanced survival compared with ATP-treated TH1 cells, suggesting autocrine action of TH17-derived IL-1β. Together these data reveal a critical role for IL-1β produced by a TH17 cell–intrinsic ASC–NLRP3–caspase-8 inflammasome during inflammation of the central nervous system.
Details
- Language :
- English
- ISSN :
- 15292908 and 15292916
- Volume :
- 17
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Nature Immunology
- Publication Type :
- Periodical
- Accession number :
- ejs38582159
- Full Text :
- https://doi.org/10.1038/ni.3389