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

Author

Listed:
  • Helen Luck

    (University Health Network
    University of Toronto
    10-352 Toronto Medical Discovery Tower)

  • Saad Khan

    (University Health Network
    University of Toronto
    10-352 Toronto Medical Discovery Tower)

  • Justin H. Kim

    (University Health Network)

  • Julia K. Copeland

    (University of Toronto)

  • Xavier S. Revelo

    (University of Minnesota
    University of Minnesota)

  • Sue Tsai

    (University Health Network
    University of Alberta)

  • Mainak Chakraborty

    (University Health Network)

  • Kathleen Cheng

    (University Health Network
    University of Toronto)

  • Yi Tao Chan

    (University Health Network
    University of Toronto)

  • Mark K. Nøhr

    (University Health Network)

  • Xavier Clemente-Casares

    (University Health Network
    University of Alberta)

  • Marie-Christine Perry

    (University of Toronto)

  • Magar Ghazarian

    (University Health Network)

  • Helena Lei

    (University Health Network)

  • Yi-Hsuan Lin

    (University Health Network
    Chang Gung University)

  • Bryan Coburn

    (University of Toronto
    University Health Network
    University of Toronto)

  • Allan Okrainec

    (University Health Network
    University of Toronto)

  • Timothy Jackson

    (University Health Network
    University of Toronto)

  • Susan Poutanen

    (University of Toronto
    University of Toronto
    University Health Network/Sinai Health System)

  • Herbert Gaisano

    (University of Toronto)

  • Johane P. Allard

    (University of Toronto
    University Health Network)

  • David S. Guttman

    (University of Toronto)

  • Margaret E. Conner

    (Baylor College of Medicine)

  • Shawn Winer

    (University of Toronto
    St. Michael’s Hospital)

  • Daniel A. Winer

    (University Health Network
    University of Toronto
    University of Toronto
    University Health Network)

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.

Suggested Citation

  • 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 , 2019. "Gut-associated IgA+ immune cells regulate obesity-related insulin resistance," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11370-y
    DOI: 10.1038/s41467-019-11370-y
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    Cited by:

    1. Pai Wang & Xin Yang & Luyao Zhang & Sha Sha & Juan Huang & Jian Peng & Jianlei Gu & James Alexander Pearson & Youjia Hu & Hongyu Zhao & F. Susan Wong & Quan Wang & Li Wen, 2024. "Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Isaac G. Crusoe & Ian C. Chiwaya & Tasnim I. Habib, 2024. "Immune Control of Gut Microbiota Prevents Obesity and the Effect of Antibiotic on Microbial Population," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 11(5), pages 1-9, May.

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