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

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

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 1

Decreased frequency of circulating MAIT cells in T2D and obesity.

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Decreased frequency of circulating MAIT cells in T2D and obesity. (A) Co...
(A) Costaining of lean and obese adults’ PBMCs with anti-Vα7.2 and anti-CD161 antibodies and with the 6-HM–loaded MR1 tetramer. All the cells binding to the MR1-6-HM tetramer were CD161hiVα7.2+, and MAIT cells were stained only by the MR1 tetramer loaded with the 6-HM ligand, and not the 6-FP ligand. MAIT cells were either CD8+ or double negative. (B) Lower frequencies of circulating MAIT cells were detected in nonobese T2D (n = 10), obese (Ob) T2D (n = 37), and non-T2D obese patients (n = 52) as compared with nondiabetic, nonobese healthy controls (n = 23). Note that in 12 obese patients, circulating MAIT cell frequency was below detection limit (<0.001%). Frequencies below 0.001% were arbitrarily displayed at 0.0005 but not included in the median and statistical calculations. †P < 0.0001. Adjusting for age and sex in a linear regression model did not change the significance. (C) Correlation between BMI and MAIT cell frequency (n = 122). (D) CD25 expression on MAIT cells in controls (n = 19) and T2D obese patients (n = 16). (E) CD69 expression on MAIT cells in controls (n = 20) and T2D obese patients (n = 14). **P < 0.003. Mann-Whitney U test and Spearman’s correlation. Straight lines represent medians. BMI is shown as kg/m2.