Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

J Clin Invest. 2015 Apr;125(4):1752-62. doi: 10.1172/JCI78941. Epub 2015 Mar 9.

Abstract

Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation, activation of immune cells, and alterations of the gut microbiota. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial ligands, are present in blood and enriched in mucosal and inflamed tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of patients with T2D and/or severe obesity. We determined that circulating MAIT cell frequency was dramatically decreased in both patient groups, and this population was even undetectable in some obese patients. Moreover, in both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were more abundant in adipose tissue than in the blood and exhibited a striking IL-17 profile. Bariatric surgery in obese patients not only improved their metabolic parameters but also increased circulating MAIT cell frequency at 3 months after surgery. Similarly, cytokine production by blood MAIT cells was strongly decreased after surgery. This study reveals profound MAIT cell abnormalities in patients harboring metabolic disorders, suggesting their potential role in these pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adipose Tissue / immunology*
  • Adult
  • Bariatric Surgery
  • Blood Cells / immunology
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Humans
  • Inflammation
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / blood
  • Leptin / blood
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Natural Killer T-Cells / immunology*
  • Obesity / blood
  • Obesity / immunology*
  • Obesity / pathology
  • Obesity / surgery
  • Omentum / immunology
  • Organ Specificity
  • Postoperative Period
  • Subcutaneous Tissue / immunology
  • T-Lymphocyte Subsets / immunology*

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Cytokines
  • Interleukin-17
  • Leptin