Touch Sothea, Assmann Karen E, Aron-Wisnewsky Judith, Marquet Florian, Rouault Christine, Fradet Magali, Mosbah Héléna, Consortium MetaCardis, Isnard Richard, Helft Gérard, Lehuen Agnès, Poitou Christine, Clément Karine, André Sébastien
Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique (UMR_S) 1166, Nutriomics Team, Paris, France.
Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpétrière Hospital, Paris, France.
FASEB J. 2018 Apr 27:fj201800052RR. doi: 10.1096/fj.201800052RR.
The disruption of systemic immune homeostasis is a key mediator in the progression of cardiometabolic diseases (CMDs). We aimed to extend knowledge regarding the clinical relevance of CMD-associated variation of circulating mucosal-associated invariant T (MAIT) cell abundance and to explore underlying cellular mechanisms. We analyzed cross-sectional data from 439 participants of the Metagenomics in Cardiometabolic Diseases (MetaCardis) study, stratified into 6 groups: healthy control subjects and patients with metabolic syndrome (MS), obesity, type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD) without, or with congestive heart failure (CAD-CHF). Blood MAIT cell frequency was significantly decreased in all CMD groups, including early (MS) and later (CAD and CAD-CHF) stages of disease progression. Reduced MAIT cell abundance was associated with increased glycosylated hemoglobin, inflammation markers, and deterioration of cardiac function. Glucose dose dependently promoted MAIT cell apoptosis in vitro, independently of anti-CD3 and cytokine-mediated activation. This outcome suggests the prominence of metabolic over an antigenic or cytokine-rich environment to promote MAIT cell reduction in patients with CMD. In summary, all stages of CMDs are characterized by reduced circulating MAIT cells. Chronically elevated blood glucose levels could contribute to this decline. These data extend the pathologic relevance of MAIT cell loss and suggest that MAIT cell abundance may serve as an indicator of cardiometabolic health.-Touch, S., Assmann, K. E., Aron-Wisnewsky, J., Marquet, F., Rouault, C., Fradet, M., Mosbah, H., MetaCardis Consortium, Isnard, R., Helft, G., Lehuen, A., Poitou, C., Clément, K., André, S. Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders.
全身免疫稳态的破坏是心脏代谢疾病（CMD）进展的关键介质。我们旨在扩展关于循环黏膜相关恒定T（MAIT）细胞丰度的CMD相关变异的临床相关性的知识，并探索潜在的细胞机制。我们分析了心脏代谢疾病宏基因组学（MetaCardis）研究中439名参与者的横断面数据，分为6组：健康对照受试者以及患有代谢综合征（MS）、肥胖症、2型糖尿病（T2DM）和冠状动脉疾病（CAD）且无或伴有充血性心力衰竭（CAD-CHF）的患者。在所有CMD组中，包括疾病进展的早期（MS）和晚期（CAD和CAD-CHF），血液MAIT细胞频率均显著降低。MAIT细胞丰度降低与糖化血红蛋白升高、炎症标志物以及心脏功能恶化有关。葡萄糖在体外剂量依赖性地促进MAIT细胞凋亡，独立于抗CD3和细胞因子介导的激活。这一结果表明，在CMD患者中，代谢因素比富含抗原或细胞因子的环境更能促进MAIT细胞减少。总之，CMD的所有阶段都以循环MAIT细胞减少为特征。长期升高的血糖水平可能导致这种下降。这些数据扩展了MAIT细胞丢失的病理相关性，并表明MAIT细胞丰度可能作为心脏代谢健康的指标。——图奇，S.，阿斯曼，K.E.，阿隆-维斯涅夫斯基，J.，马尔凯，F.，鲁奥，C.，弗拉代，M.，莫斯巴赫，H.，MetaCardis联盟，伊萨尔，R.，埃尔夫特，G.，勒于恩，A.，普瓦图，C.，克莱芒，K.，安德烈，S.黏膜相关恒定T（MAIT）细胞在心脏代谢紊乱中减少且易于凋亡。
