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

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.

SUBMITTER: Giannoudaki E

PROVIDER: S-EPMC6728358 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Giannoudaki Eirini E Hernandez-Santana Yasmina E YE Mulfaul Kelly K Doyle Sarah L SL Hams Emily E Fallon Padraic G PG Mat Arimin A O'Shea Donal D Kopf Manfred M Hogan Andrew E AE Walsh Patrick T PT

Nature communications 20190905 1

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 antag ...[more]

PMID: 31488830

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Dataset Information

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

Publications

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

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