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    Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction.

    Giannoudaki, Eirini and Hernandez-Santana, Yasmina E. and Mulfaul, Kelly and Doyle, Sarah L. and Hams, Emily and Fallon, Padraic G. and Mat, Arimin and O'Shea, Donal and Kopf, Manfred and Hogan, Andrew and Walsh, Patrick T. (2019) Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction. Nature Communications, 10 (4003). ISSN 2041-1723

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    Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes. Mice lacking IL-36Ra, an IL-36 family signalling antagonist, develop less diet-induced weight gain, hyperglycemia and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.

    Item Type: Article
    Additional Information: Funding: This work was supported by grant funding from the National Children’s Research Centre and the Health Research Board, Ireland (HRA-POR-2015-1066) to P.T.W. and a Swiss National Science Foundation grant (310030_163443/1) to M.K. Cite as: Giannoudaki, E., Hernandez-Santana, Y.E., Mulfaul, K. et al. Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction. Nat Commun 10, 4003 (2019). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit licenses/by/4.0/.
    Keywords: Interleukin-36; cytokines; intestinal microbiome; protect obesity; metabolic dysfunction;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 13971
    Identification Number:
    Depositing User: Andrew Hogan
    Date Deposited: 08 Feb 2021 16:31
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    Funders: National Children’s Research Centre, Health Research Board (HRB), Swiss National Science Foundation

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