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. Rothenberg; Amy G. Hise; George R. Dubyak; Richard M. Ransohoff; Xiaoxia Li

doi:10.1038/ni.3389

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 journal › Article › peer-review

106 Scopus citations

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.

Original language	English (US)
Pages (from-to)	583-592
Number of pages	10
Journal	Nature Immunology
Volume	17
Issue number	5
DOIs	https://doi.org/10.1038/ni.3389
State	Published - May 1 2016
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Martin, B. N., Wang, C., Zhang, C. J., Kang, Z., Gulen, M. F., Zepp, J. A., Zhao, J., Bian, G., Do, J. S., Min, B., Pavicic, P. G., El-Sanadi, C., Fox, P. L., Akitsu, A., Iwakura, Y., Sarkar, A., Wewers, M. D., Kaiser, W. J., Mocarski, E. S., ... Li, X. (2016). T cell-intrinsic ASC critically promotes T H 17-mediated experimental autoimmune encephalomyelitis. Nature Immunology, 17(5), 583-592. https://doi.org/10.1038/ni.3389

@article{356ff820f73249a18fc6f8e38d7185c9,

title = "T cell-intrinsic ASC critically promotes T H 17-mediated experimental autoimmune encephalomyelitis",

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.",

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

note = "Funding Information: This investigation was supported by the National Multiple Sclerosis Society (grant RG5130A2/1 to X.L.) and the US National Institutes of Health (grants 5R01NS071996-05, 1RO1AA023722 and MSTP-T32GM007250 to X.L.). Publisher Copyright: {\textcopyright} 2016 Nature America, Inc. All rights reserved.",

year = "2016",

month = may,

day = "1",

doi = "10.1038/ni.3389",

language = "English (US)",

volume = "17",

pages = "583--592",

journal = "Nature Immunology",

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Martin, BN, Wang, C, Zhang, CJ, Kang, Z, Gulen, MF, Zepp, JA, Zhao, J, Bian, G, Do, JS, Min, B, Pavicic, PG, El-Sanadi, C, Fox, PL, Akitsu, A, Iwakura, Y, Sarkar, A, Wewers, MD, Kaiser, WJ, Mocarski, ES, Rothenberg, ME, Hise, AG, Dubyak, GR, Ransohoff, RM & Li, X 2016, 'T cell-intrinsic ASC critically promotes T H 17-mediated experimental autoimmune encephalomyelitis', Nature Immunology, vol. 17, no. 5, pp. 583-592. https://doi.org/10.1038/ni.3389

TY - JOUR

T1 - T cell-intrinsic ASC critically promotes T H 17-mediated experimental autoimmune encephalomyelitis

AU - Martin, Bradley N.

AU - Wang, Chenhui

AU - Zhang, Cun Jin

AU - Kang, Zizhen

AU - Gulen, Muhammet Fatih

AU - Zepp, Jarod A.

AU - Zhao, Junjie

AU - Bian, Guanglin

AU - Do, Jeong Su

AU - Min, Booki

AU - Pavicic, Paul G.

AU - El-Sanadi, Caroline

AU - Fox, Paul L.

AU - Akitsu, Aoi

AU - Iwakura, Yoichiro

AU - Sarkar, Anasuya

AU - Wewers, Mark D.

AU - Kaiser, William J.

AU - Mocarski, Edward S.

AU - Rothenberg, Marc E.

AU - Hise, Amy G.

AU - Dubyak, George R.

AU - Ransohoff, Richard M.

AU - Li, Xiaoxia

N1 - Funding Information: This investigation was supported by the National Multiple Sclerosis Society (grant RG5130A2/1 to X.L.) and the US National Institutes of Health (grants 5R01NS071996-05, 1RO1AA023722 and MSTP-T32GM007250 to X.L.). Publisher Copyright: © 2016 Nature America, Inc. All rights reserved.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

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JO - Nature Immunology

JF - Nature Immunology

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ER -

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

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