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Nat Immunol. 2016 May;17(5):583-92. doi: 10.1038/ni.3389. Epub 2016 Mar 21.

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

Author information

1
Department of Immunology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
2
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
3
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
4
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
5
Department of Immunology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
6
Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
7
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
8
Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
9
Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki, Noda, Japan.
10
Davis Heart and Lung Research Institute, Ohio State University College of Medicine, Columbus, Ohio, USA.
11
Department of Microbiology and Immunology, Emory Vaccine Center, Atlanta, Georgia, USA.
12
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
13
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
14
Department of Neurosciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.

Abstract

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.

PMID:
26998763
PMCID:
PMC5385929
DOI:
10.1038/ni.3389
[Indexed for MEDLINE]
Free PMC Article

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