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    Interleukin 37 expression protects mice from colitis


    McNamee, Eóin N. and Masterson, Joanne C. and Jedlicka, Paul and McManus, Martine and Grenz, Almut and Collins, Colm B. and Nold, Marcel F. and Nold-Petry, Claudia and Bufler, Philip and Dinarello, Charles A. and Rivera-Nieves, Jesus (2011) Interleukin 37 expression protects mice from colitis. Proceedings of the National Academy of Sciences of the United States of America, 108 (40). pp. 16711-16716. ISSN 0027-8424

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    Abstract

    IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P < 0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P < 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1β and TNFα from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P £ 0.005), whereas IL-10 was increased sixfold (P < 0.001). However, IL-10 was not required for the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient to exert anti-inflammatory effects because WT mice reconstituted with hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key modulator of intestinal inflammation.

    Item Type: Article
    Keywords: Interleukin 37 expression; protects mice; colitis; cytokine; intestine; inflammatory bowel disease;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12499
    Identification Number: https://doi.org/10.1073/pnas.1111982108
    Depositing User: Joanne Masterson
    Date Deposited: 27 Feb 2020 16:39
    Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
    Publisher: National Academy of Sciences
    Refereed: Yes
    URI:

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