Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co Kildare, Ireland.
National Children's Research Centre, Dublin 12, Ireland.
Sci Signal. 2023 Apr 18;16(781):eabo2709. doi: 10.1126/scisignal.abo2709.
Mucosal-associated invariant T (MAIT) cells are an abundant population of innate T cells that recognize bacterial ligands and play a key role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells undergo proliferative expansion and increase their production of effector molecules such as cytokines. In this study, we found that both mRNA and protein abundance of the key metabolism regulator and transcription factor MYC was increased in stimulated MAIT cells. Using quantitative mass spectrometry, we identified the activation of two MYC-controlled metabolic pathways, amino acid transport and glycolysis, both of which were necessary for MAIT cell proliferation. Last, we showed that MAIT cells isolated from people with obesity showed decreased mRNA abundance upon activation, which was associated with defective MAIT cell proliferation and functional responses. Collectively, our data uncover the importance of MYC-regulated metabolism for MAIT cell proliferation and provide additional insight into the molecular basis for the functional defects of MAIT cells in obesity.
黏膜相关恒定 T(MAIT)细胞是一类丰富的先天 T 细胞,能够识别细菌配体,并在宿主抵抗细菌和病毒病原体的过程中发挥关键作用。在活化后,MAIT 细胞经历增殖扩张,并增加细胞因子等效应分子的产生。在这项研究中,我们发现,在受刺激的 MAIT 细胞中,关键代谢调节因子和转录因子 MYC 的 mRNA 和蛋白丰度均增加。通过定量质谱分析,我们鉴定了两种 MYC 控制的代谢途径的激活,即氨基酸转运和糖酵解,这两种途径均对 MAIT 细胞增殖是必需的。最后,我们表明,从肥胖人群中分离出的 MAIT 细胞在活化时其 mRNA 丰度降低,这与 MAIT 细胞增殖和功能反应的缺陷有关。总之,我们的数据揭示了 MYC 调控的代谢对 MAIT 细胞增殖的重要性,并为肥胖症中 MAIT 细胞功能缺陷的分子基础提供了更多的见解。