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肥胖和2型糖尿病患者黏膜相关恒定T细胞的改变

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

作者信息

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

出版信息

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.

摘要

肥胖症和2型糖尿病(T2D)与低度炎症、免疫细胞激活及肠道微生物群改变有关。黏膜相关恒定T(MAIT)细胞是识别细菌配体的固有样T细胞,存在于血液中,在黏膜和炎症组织中富集。在此,我们分析了T2D和/或重度肥胖患者血液和脂肪组织中的MAIT细胞。我们确定,两个患者组的循环MAIT细胞频率均显著降低,且在一些肥胖患者中甚至检测不到该细胞群。此外,在两个患者组中,循环MAIT细胞均表现出与Th1和Th17细胞因子产生增加相关的激活表型。在肥胖患者中,MAIT细胞在脂肪组织中比在血液中更丰富,并呈现出显著的IL-17特征。肥胖患者接受减肥手术后,不仅改善了代谢参数,还在术后3个月时增加了循环MAIT细胞频率。同样,术后血液MAIT细胞产生的细胞因子也大幅减少。这项研究揭示了患有代谢紊乱患者中MAIT细胞存在严重异常,提示它们在这些病症中可能发挥的作用。

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