| First Author | Luck H | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 3650 |
| PubMed ID | 31409776 | Mgi Jnum | J:279392 |
| Mgi Id | MGI:6362405 | Doi | 10.1038/s41467-019-11370-y |
| Citation | Luck H, et al. (2019) Gut-associated IgA(+) immune cells regulate obesity-related insulin resistance. Nat Commun 10(1):3650 |
| abstractText | 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. |
