期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-11370-y
关键词
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资金
- Canadian Institutes of Health Research (CIHR) [119414, 142708, 148385]
- Diabetes Canada [OG-3-15-5014]
- Canadian Liver Foundation (CLF)
- CIHR [303157]
- Canada Research Chair
- Ontario Ministry of Innovation Early Researcher Award
- Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST)/Aventis Pasteur
- Banting and Best Diabetes Centre (BBDC) Graduate Scholarship
- CIHR Canada Graduate Scholarship-Doctoral (CGS-D) Award
- UTRS [152465]
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.
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