Li Fei, Feng Yu, Yin Zesheng, Wang Yahong
Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
School of Public Health, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2025 Jul 31;26(15):7400. doi: 10.3390/ijms26157400.
T cells play a vital role in resisting pathogen invasion and maintaining immune homeostasis. However, T cells gradually become exhausted under chronic antigenic stimulation, and this exhaustion is closely related to mitochondrial dysfunction in T cells. Mitochondria play a crucial role in the metabolic reprogramming of T cells to achieve the desired immune response. Here, we compiled the latest research on how mitochondrial metabolism determines T cell function and differentiation, with the mechanisms mainly including mitochondrial biogenesis, fission, fusion, mitophagy, and mitochondrial transfer. In addition, the alterations in mitochondrial metabolism in T-cell exhaustion were also reviewed. Furthermore, we discussed intervention strategies targeting mitochondrial metabolism to reverse T cell exhaustion in detail, including inducing PGC-1α expression, alleviating reactive oxygen species (ROS) production or hypoxia, enhancing ATP production, and utilizing mitochondrial transfer. Targeting mitochondrial metabolism in exhausted T cells may achieve the goal of reversing and preventing T cell exhaustion.
T细胞在抵抗病原体入侵和维持免疫稳态中发挥着至关重要的作用。然而,在慢性抗原刺激下,T细胞会逐渐耗竭,而这种耗竭与T细胞中的线粒体功能障碍密切相关。线粒体在T细胞的代谢重编程中发挥着关键作用,以实现所需的免疫反应。在此,我们汇总了关于线粒体代谢如何决定T细胞功能和分化的最新研究,其机制主要包括线粒体生物发生、裂变、融合、线粒体自噬和线粒体转移。此外,还综述了T细胞耗竭中线粒体代谢的改变。此外,我们详细讨论了针对线粒体代谢以逆转T细胞耗竭的干预策略,包括诱导PGC-1α表达、减轻活性氧(ROS)产生或缺氧、增强ATP产生以及利用线粒体转移。针对耗竭T细胞中的线粒体代谢可能实现逆转和预防T细胞耗竭的目标。
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