Gut-associated IgA+ immune cells regulate obesity-related insulin resistance
Luck H, Khan S, Kim JH, Copeland JK, Revelo XS, Tsai S, Chakraborty M, Cheng K, Chan YT, Nøhr MK, Clemente-Casares X, Perry M-C, Ghazarian M, Lei H, Lin Y-H, Coburn B, Okrainec A, Jackson T, Poutanen S, Gaisano H, Allard JP, Guttman DS, Conner ME, Winer S, Winer DA (2019) Nat Commun 2019; 10, 3650; DOI 10.1038/s41467-019-11370-y
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.
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