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

Author

Listed:
  • Eirini Giannoudaki

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

  • Yasmina E. Hernandez-Santana

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

  • Kelly Mulfaul

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

  • Sarah L. Doyle

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

  • Emily Hams

    (Trinity College Dublin)

  • Padraic G. Fallon

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

  • Arimin Mat

    (Obesity Immunology Research, St Vincent’s University Hospital and University College Dublin)

  • Donal O’Shea

    (Obesity Immunology Research, St Vincent’s University Hospital and University College Dublin)

  • Manfred Kopf

    (ETH Zurich)

  • Andrew E. Hogan

    (National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin
    National University of Ireland)

  • Patrick T. Walsh

    (Trinity College Dublin
    National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin)

Abstract

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.

Suggested Citation

  • Eirini Giannoudaki & Yasmina E. Hernandez-Santana & Kelly Mulfaul & Sarah L. Doyle & Emily Hams & Padraic G. Fallon & Arimin Mat & Donal O’Shea & Manfred Kopf & Andrew E. Hogan & Patrick T. Walsh, 2019. "Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11944-w
    DOI: 10.1038/s41467-019-11944-w
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    Cited by:

    1. Yoshihiro Hayashi & Yasushige Kamimura-Aoyagi & Sayuri Nishikawa & Rena Noka & Rika Iwata & Asami Iwabuchi & Yushin Watanabe & Natsumi Matsunuma & Kanako Yuki & Hiroki Kobayashi & Yuka Harada & Hirono, 2024. "IL36G-producing neutrophil-like monocytes promote cachexia in cancer," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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