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Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients
Isabelle Magalhaes, … , Karine Clément, Agnès Lehuen
Isabelle Magalhaes, … , Karine Clément, Agnès Lehuen
Published March 9, 2015
Citation Information: J Clin Invest. 2015;125(4):1752-1762. https://doi.org/10.1172/JCI78941.
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Research Article Immunology

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

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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.

Authors

Isabelle Magalhaes, Karine Pingris, Christine Poitou, Stéphanie Bessoles, Nicolas Venteclef, Badr Kiaf, Lucie Beaudoin, Jennifer Da Silva, Omran Allatif, Jamie Rossjohn, Lars Kjer-Nielsen, James McCluskey, Séverine Ledoux, Laurent Genser, Adriana Torcivia, Claire Soudais, Olivier Lantz, Christian Boitard, Judith Aron-Wisnewsky, Etienne Larger, Karine Clément, Agnès Lehuen

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Figure 6

Influence of AT samples on MAIT cell phenotype.

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Influence of AT samples on MAIT cell phenotype.
(A) PBMCs from healthy d...
(A) PBMCs from healthy donors were cocultured with AT samples from obese patients, followed by flow cytometric analysis of Bcl-2 expression in MAIT cells. (B–D) Flow cytometric analysis of Bcl-2 and Ki-67 expression in MAIT cells. (B and C) Bcl-2 MFI and percent of Ki-67 expression in MAIT cells from peripheral blood and OM AT of 5 obese patients. (D) Bcl-2 MFI in Ki-67– and Ki-67+ MAIT cells from AT. MFI, median fluorescence intensity.

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