{"title":"重塑 T 细胞线粒体代谢,治疗自身免疫性疾病。","authors":"","doi":"10.1016/j.autrev.2024.103583","DOIUrl":null,"url":null,"abstract":"<div><p>T cells are key drivers of the pathogenesis of autoimmune diseases by producing cytokines, stimulating the generation of autoantibodies, and mediating tissue and cell damage. Distinct mitochondrial metabolic pathways govern the direction of T-cell differentiation and function and rely on specific nutrients and metabolic enzymes. Metabolic substrate uptake and mitochondrial metabolism form the foundational elements for T-cell activation, proliferation, differentiation, and effector function, contributing to the dynamic interplay between immunological signals and mitochondrial metabolism in coordinating adaptive immunity. Perturbations in substrate availability and enzyme activity may impair T-cell immunosuppressive function, fostering autoreactive responses and disrupting immune homeostasis, ultimately contributing to autoimmune disease pathogenesis. A growing body of studies has explored how metabolic processes regulate the function of diverse T-cell subsets in autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune hepatitis (AIH), inflammatory bowel disease (IBD), and psoriasis. This review describes the coordination of T-cell biology by mitochondrial metabolism, including the electron transport chain (ETC), oxidative phosphorylation, amino acid metabolism, fatty acid metabolism, and one‑carbon metabolism. This study elucidated the intricate crosstalk between mitochondrial metabolic programs, signal transduction pathways, and transcription factors. This review summarizes potential therapeutic targets for T-cell mitochondrial metabolism and signaling in autoimmune diseases, providing insights for future studies.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000740/pdfft?md5=6bb063881495178bffec26ec237556aa&pid=1-s2.0-S1568997224000740-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Remodeling of T-cell mitochondrial metabolism to treat autoimmune diseases\",\"authors\":\"\",\"doi\":\"10.1016/j.autrev.2024.103583\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>T cells are key drivers of the pathogenesis of autoimmune diseases by producing cytokines, stimulating the generation of autoantibodies, and mediating tissue and cell damage. Distinct mitochondrial metabolic pathways govern the direction of T-cell differentiation and function and rely on specific nutrients and metabolic enzymes. Metabolic substrate uptake and mitochondrial metabolism form the foundational elements for T-cell activation, proliferation, differentiation, and effector function, contributing to the dynamic interplay between immunological signals and mitochondrial metabolism in coordinating adaptive immunity. Perturbations in substrate availability and enzyme activity may impair T-cell immunosuppressive function, fostering autoreactive responses and disrupting immune homeostasis, ultimately contributing to autoimmune disease pathogenesis. A growing body of studies has explored how metabolic processes regulate the function of diverse T-cell subsets in autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune hepatitis (AIH), inflammatory bowel disease (IBD), and psoriasis. This review describes the coordination of T-cell biology by mitochondrial metabolism, including the electron transport chain (ETC), oxidative phosphorylation, amino acid metabolism, fatty acid metabolism, and one‑carbon metabolism. This study elucidated the intricate crosstalk between mitochondrial metabolic programs, signal transduction pathways, and transcription factors. 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引用次数: 0
摘要
T 细胞通过产生细胞因子、刺激自身抗体的产生以及介导组织和细胞损伤,是自身免疫性疾病发病机制的关键驱动因素。不同的线粒体代谢途径决定着 T 细胞分化和功能的方向,并依赖于特定的营养物质和代谢酶。代谢底物摄取和线粒体代谢是 T 细胞活化、增殖、分化和效应功能的基本要素,有助于免疫信号和线粒体代谢在协调适应性免疫中的动态相互作用。底物可用性和酶活性的紊乱可能会损害 T 细胞的免疫抑制功能,助长自体反应,破坏免疫平衡,最终导致自身免疫性疾病的发病。越来越多的研究探讨了新陈代谢过程如何调节系统性红斑狼疮(SLE)、多发性硬化症(MS)、自身免疫性肝炎(AIH)、炎症性肠病(IBD)和银屑病等自身免疫性疾病中不同 T 细胞亚群的功能。这篇综述介绍了线粒体代谢对 T 细胞生物学的协调作用,包括电子传递链(ETC)、氧化磷酸化、氨基酸代谢、脂肪酸代谢和一碳代谢。这项研究阐明了线粒体代谢程序、信号转导途径和转录因子之间错综复杂的相互关系。本综述总结了自身免疫性疾病中 T 细胞线粒体代谢和信号转导的潜在治疗靶点,为今后的研究提供了启示。
Remodeling of T-cell mitochondrial metabolism to treat autoimmune diseases
T cells are key drivers of the pathogenesis of autoimmune diseases by producing cytokines, stimulating the generation of autoantibodies, and mediating tissue and cell damage. Distinct mitochondrial metabolic pathways govern the direction of T-cell differentiation and function and rely on specific nutrients and metabolic enzymes. Metabolic substrate uptake and mitochondrial metabolism form the foundational elements for T-cell activation, proliferation, differentiation, and effector function, contributing to the dynamic interplay between immunological signals and mitochondrial metabolism in coordinating adaptive immunity. Perturbations in substrate availability and enzyme activity may impair T-cell immunosuppressive function, fostering autoreactive responses and disrupting immune homeostasis, ultimately contributing to autoimmune disease pathogenesis. A growing body of studies has explored how metabolic processes regulate the function of diverse T-cell subsets in autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune hepatitis (AIH), inflammatory bowel disease (IBD), and psoriasis. This review describes the coordination of T-cell biology by mitochondrial metabolism, including the electron transport chain (ETC), oxidative phosphorylation, amino acid metabolism, fatty acid metabolism, and one‑carbon metabolism. This study elucidated the intricate crosstalk between mitochondrial metabolic programs, signal transduction pathways, and transcription factors. This review summarizes potential therapeutic targets for T-cell mitochondrial metabolism and signaling in autoimmune diseases, providing insights for future studies.
期刊介绍:
Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers.
The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences.
In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations.
Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.