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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Helen Luck
  • Saad Khan
  • Justin H Kim
  • Julia K Copeland
  • Xavier S Revelo
  • Sue Tsai
  • Mainak Chakraborty
  • Kathleen Cheng
  • Yi Tao Chan
  • 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
  • Daniel A Winer

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.

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind10
Udgave nummer1
Sider (fra-til)3650
ISSN2041-1723
DOI
StatusUdgivet - 13 aug. 2019

ID: 225793011