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 Jr; Caroline El-Sanadi; Paul L Fox; Aoi Akitsu; Yoichiro Iwakura; Anasuya Sarkar; Mark D Wewers; William J Kaiser; Edward S Mocarski; Marc E Rothenberg; Amy G Hise; George R Dubyak; Richard M Ransohoff; Xiaoxia Li

doi:10.1038/ni.3389

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

Journal article

Open access

Peer reviewed

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, …

Nature immunology, Vol.17(5), pp.583-592

05/2016

DOI: 10.1038/ni.3389

PMCID: PMC5385929

PMID: 26998763

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https://www.ncbi.nlm.nih.gov/pmc/articles/5385929View

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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.

Flow Cytometry

Adenosine Triphosphate - pharmacology

Animals

Apoptosis Regulatory Proteins - genetics

Apoptosis Regulatory Proteins - immunology

Apoptosis Regulatory Proteins - metabolism

CARD Signaling Adaptor Proteins

Carrier Proteins - genetics

Carrier Proteins - immunology

Carrier Proteins - metabolism

Caspase 8 - genetics

Caspase 8 - immunology

Caspase 8 - metabolism

CD4-Positive T-Lymphocytes - immunology

CD4-Positive T-Lymphocytes - metabolism

Cell Survival - genetics

Cell Survival - immunology

Cells, Cultured

Encephalomyelitis, Autoimmune, Experimental - genetics

Encephalomyelitis, Autoimmune, Experimental - immunology

Encephalomyelitis, Autoimmune, Experimental - metabolism

Gene Expression - immunology

Immunoblotting

Inflammasomes - genetics

Inflammasomes - immunology

Inflammasomes - metabolism

Interleukin-17 - genetics

Interleukin-17 - immunology

Interleukin-17 - metabolism

Interleukin-1beta - genetics

Interleukin-1beta - immunology

Interleukin-1beta - metabolism

Mice, Inbred C57BL

Mice, Knockout

Mice, Transgenic

NLR Family, Pyrin Domain-Containing 3 Protein

Reverse Transcriptase Polymerase Chain Reaction

Signal Transduction - genetics

Signal Transduction - immunology

T-Lymphocytes - drug effects

T-Lymphocytes - immunology

T-Lymphocytes - metabolism

Th17 Cells - drug effects

Th17 Cells - immunology

Th17 Cells - metabolism

Details

Title: Subtitle: T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis
Creators: Bradley N Martin - Case Western Reserve University
Chenhui Wang - Cleveland Clinic
Cun-jin Zhang - Tianjin Medical University
Zizhen Kang - Shanghai Jiao Tong University
Muhammet Fatih Gulen - Cleveland Clinic
Jarod A Zepp - Cleveland Clinic
Junjie Zhao - Cleveland Clinic
Guanglin Bian - Cleveland Clinic
Jeong-su Do - Cleveland Clinic
Booki Min - Cleveland Clinic
Paul G Pavicic Jr - Cleveland Clinic
Caroline El-Sanadi - Case Western Reserve University
Paul L Fox - Cleveland Clinic
Aoi Akitsu - Tokyo University of Science
Yoichiro Iwakura - Tokyo University of Science
Anasuya Sarkar - Ohio State University
Mark D Wewers - Ohio State University
William J Kaiser - Emory University
Edward S Mocarski - Emory University
Marc E Rothenberg - Cincinnati Children's Hospital Medical Center
Amy G Hise - Case Western Reserve University
George R Dubyak - Case Western Reserve University
Richard M Ransohoff - Cleveland Clinic
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: Nature immunology, Vol.17(5), pp.583-592
DOI: 10.1038/ni.3389
PMID: 26998763
PMCID: PMC5385929
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Grant note: P01 HL103453 / NHLBI NIH HHS T32 HL007843 / NHLBI NIH HHS R01 AI118853 / NIAID NIH HHS 5R01NS071996-05 / NINDS NIH HHS U10 HL109250 / NHLBI NIH HHS R01 DE018279 / NIDCR NIH HHS R01 AA023722 / NIAAA NIH HHS 1R01AA023722 / NIAAA NIH HHS P01 HL029582 / NHLBI NIH HHS DP5 OD012198 / NIH HHS P01 CA062220 / NCI NIH HHS T32GM007250 / NIGMS NIH HHS R01 GM036387 / NIGMS NIH HHS T32 GM007250 / NIGMS NIH HHS R01 NS071996 / NINDS NIH HHS I01 BX002607 / BLRD VA
Language: English
Date published: 05/2016
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201254602771

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