Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
Front Immunol. 2023 Jun 29;14:1211221. doi: 10.3389/fimmu.2023.1211221. eCollection 2023.
Cellular metabolism plays a critical role in determining the fate and function of cells. Metabolic reprogramming and its byproducts have a complex impact on cellular activities. In quiescent T cells, oxidative phosphorylation (OXPHOS) is the primary pathway for survival. However, upon antigen activation, T cells undergo rapid metabolic reprogramming, characterized by an elevation in both glycolysis and OXPHOS. While both pathways are induced, the balance predominantly shifts towards glycolysis, enabling T cells to rapidly proliferate and enhance their functionality, representing the most distinctive signature during activation. Metabolic processes generate various small molecules resulting from enzyme-catalyzed reactions, which also modulate protein function and exert regulatory control. Notably, recent studies have revealed the direct modification of histones, known as lactylation, by lactate derived from glycolysis. This lactylation process influences gene transcription and adds a novel variable to the regulation of gene expression. Protein lactylation has been identified as an essential mechanism by which lactate exerts its diverse functions, contributing to crucial biological processes such as uterine remodeling, tumor proliferation, neural system regulation, and metabolic regulation. This review focuses on the metabolic reprogramming of T cells, explores the interplay between lactate and the immune system, highlights the impact of lactylation on cellular function, and elucidates the intersection of metabolic reprogramming and epigenetics.
细胞代谢在决定细胞命运和功能方面起着关键作用。代谢重编程及其副产物对细胞活动有复杂的影响。在静止的 T 细胞中，氧化磷酸化 (OXPHOS) 是生存的主要途径。然而，在抗原激活后，T 细胞经历快速的代谢重编程，其特征是糖酵解和 OXPHOS 均升高。虽然两条途径都被诱导，但平衡主要向糖酵解倾斜，使 T 细胞能够快速增殖并增强其功能，这是激活过程中最显著的特征。代谢过程产生各种小分子，这些小分子是由酶催化反应产生的，它们还调节蛋白质功能并发挥调节控制作用。值得注意的是，最近的研究揭示了糖酵解产生的乳酸直接修饰组蛋白，即乳酰化。这个乳酰化过程影响基因转录，并为基因表达的调控增加了一个新的变量。蛋白乳酰化已被确定为乳酸发挥其多种功能的一种重要机制，有助于子宫重塑、肿瘤增殖、神经系统调节和代谢调节等重要的生物学过程。本文综述了 T 细胞的代谢重编程，探讨了乳酸与免疫系统之间的相互作用，强调了乳酰化对细胞功能的影响，并阐明了代谢重编程和表观遗传学的交叉点。
