Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nat Chem Biol. 2022 May;18(5):470-481. doi: 10.1038/s41589-022-01017-3. Epub 2022 Apr 28.
T cells orchestrate adaptive immunity against pathogens and other immune challenges, but their dysfunction can also mediate the pathogenesis of cancer and autoimmunity. Metabolic adaptation in response to immunological and microenvironmental signals contributes to T cell function and fate decision. Lipid metabolism has emerged as a key regulator of T cell responses, with selective lipid metabolites serving as metabolic rheostats to integrate environmental cues and interplay with intracellular signaling processes. Here, we discuss how extracellular, de novo synthesized and membrane lipids orchestrate T cell biology. We also describe the roles of lipids as regulators of intracellular signaling at the levels of transcriptional, epigenetic and post-translational regulation in T cells. Finally, we summarize therapeutic targeting of lipid metabolism and signaling, and conclude with a discussion of important future directions. Understanding the molecular and functional interplay between lipid metabolism and T cell biology will ultimately inform therapeutic intervention for human disease.
T 细胞在病原体和其他免疫挑战中协调适应性免疫,但它们的功能障碍也可能介导癌症和自身免疫的发病机制。对免疫和微环境信号的代谢适应有助于 T 细胞的功能和命运决定。脂代谢已成为 T 细胞反应的关键调节剂,选择性脂质代谢物作为代谢变阻器,整合环境线索并与细胞内信号转导过程相互作用。在这里,我们讨论了细胞外、从头合成和膜脂质如何协调 T 细胞生物学。我们还描述了脂质作为 T 细胞中转录、表观遗传和翻译后水平的细胞内信号转导调节剂的作用。最后,我们总结了脂质代谢和信号转导的治疗靶向,并讨论了未来的重要方向。了解脂代谢和 T 细胞生物学之间的分子和功能相互作用将最终为人类疾病的治疗干预提供信息。