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

Bradley N. Martin, Chenhui Wang, Cun Jin Zhang, Zizhen Kang, Muhammet Fatih Gulen, Jarod A. Zepp, Junjie Zhao, Guanglin Bian, Jeong Su Do, Booki Min, Paul G. Pavicic, Caroline El-Sanadi, Paul L. Fox, Aoi Akitsu, Yoichiro Iwakura, Anasuya Sarkar, Mark D. Wewers, William J. Kaiser, Edward S. Mocarski, Marc E. RothenbergAmy G. Hise, George R. Dubyak, Richard M. Ransohoff, Xiaoxia Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


Interleukin 1β (IL-1β) 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-1β during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1β production during T H 17-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 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-1β. Together these data reveal a critical role for IL-1β produced by a T H 17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system.

Original languageEnglish (US)
Pages (from-to)583-592
Number of pages10
JournalNature Immunology
Issue number5
StatePublished - May 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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