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    Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis


    Li, Sheng and Wu, Yuqing and Yang, Dongxue and Wu, Chunyan and Ma, Chunmei and Liu, Xue and Moynagh, Paul N. and Wang, Bingwei and Hu, Gang and Yang, Shuo (2019) Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis. Journal of Experimental Medicine, 216 (11). pp. 2562-2581. ISSN 0022-1007

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    Abstract

    The NLRP3 inflammasome is critical for EAE pathogenesis; however, the role of gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome, in EAE has not been well defined. Here, we observed that the levels of GSDMD protein were greatly enhanced in the CNS of EAE mice, especially near the areas surrounding blood vessels. GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS, leading to the suppression of neuroinflammation and demyelination. Furthermore, the loss of GSDMD reduced the activation and differentiation of T cell in the secondary lymphoid organs and prevented T cell infiltration into CNS of EAE. The administration of inflammasome-related cytokines partially rescued the impairment of pathogenesis of EAE in GSDMD KO mice. Collectively, these findings provide the first demonstration of GSDMD in peripheral myeloid cells driving neuroinflammation during EAE pathogenesis.

    Item Type: Article
    Additional Information: © 2019 Crown copyright. The government of Australia, Canada, or the UK ("the Crown") owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/ licenses/by/4.0/). Cite as: Li S, Wu Y, Yang D, Wu C, Ma C, Liu X, Moynagh PN, Wang B, Hu G, Yang S. Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis. J Exp Med. 2019 Nov 4;216(11):2562-2581. doi: 10.1084/jem.20190377. Epub 2019 Aug 29. PMID: 31467036; PMCID: PMC6829591.
    Keywords: Gasdermin D; peripheral myeloid cells; neuroinflammation; experimental autoimmune encephalomyelitis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 13451
    Identification Number: https://doi.org/10.1084/jem.20190377
    Depositing User: Professor Paul Moynagh
    Date Deposited: 23 Oct 2020 14:20
    Journal or Publication Title: Journal of Experimental Medicine
    Publisher: Rockefeller University Press
    Refereed: Yes
    URI:

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