Gut-associated IgA+ immune cells regulate obesity-related insulin resistance

Helen Luck, Saad Khan, Justin H. Kim, Julia K. Copeland, Xavier S. Revelo, Sue Tsai, Mainak Chakraborty, Kathleen Cheng, Yi Tao Chan, Mark K. Nøhr, Xavier Clemente-Casares, Marie-Christine Perry, Magar Ghazarian, Helena Lei, Yi-Hsuan Lin, Bryan Coburn, Allan Okrainec, Timothy Jackson, Susan Poutanen, Herbert Gaisano, Johane P. Allard, David S. Guttman, Margaret E. Conner, Shawn Winer and Daniel A. Winer ()
Additional contact information
Helen Luck: University Health Network
Saad Khan: University Health Network
Justin H. Kim: University Health Network
Julia K. Copeland: University of Toronto
Xavier S. Revelo: University of Minnesota
Sue Tsai: University Health Network
Mainak Chakraborty: University Health Network
Kathleen Cheng: University Health Network
Yi Tao Chan: University Health Network
Mark K. Nøhr: University Health Network
Xavier Clemente-Casares: University Health Network
Marie-Christine Perry: University of Toronto
Magar Ghazarian: University Health Network
Helena Lei: University Health Network
Yi-Hsuan Lin: University Health Network
Bryan Coburn: University of Toronto
Allan Okrainec: University Health Network
Timothy Jackson: University Health Network
Susan Poutanen: University of Toronto
Herbert Gaisano: University of Toronto
Johane P. Allard: University of Toronto
David S. Guttman: University of Toronto
Margaret E. Conner: Baylor College of Medicine
Shawn Winer: University of Toronto
Daniel A. Winer: University Health Network

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract The intestinal immune system is emerging as an important contributor to obesity-related insulin resistance, but the role of intestinal B cells in this context is unclear. Here, we show that high fat diet (HFD) feeding alters intestinal IgA+ immune cells and that IgA is a critical immune regulator of glucose homeostasis. Obese mice have fewer IgA+ immune cells and less secretory IgA and IgA-promoting immune mediators. HFD-fed IgA-deficient mice have dysfunctional glucose metabolism, a phenotype that can be recapitulated by adoptive transfer of intestinal-associated pan-B cells. Mechanistically, IgA is a crucial link that controls intestinal and adipose tissue inflammation, intestinal permeability, microbial encroachment and the composition of the intestinal microbiome during HFD. Current glucose-lowering therapies, including metformin, affect intestinal-related IgA+ B cell populations in mice, while bariatric surgery regimen alters the level of fecal secretory IgA in humans. These findings identify intestinal IgA+ immune cells as mucosal mediators of whole-body glucose regulation in diet-induced metabolic disease.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11370-y

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DOI: 10.1038/s41467-019-11370-y

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