Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Genes (Basel). 2021 May 13;12(5):728. doi: 10.3390/genes12050728.
The mechanistic target of rapamycin (mTOR) controls cell fate and responses via its functions in regulating metabolism. Its role in controlling immunity was unraveled by early studies on the immunosuppressive properties of rapamycin. Recent studies have provided insights on how metabolic reprogramming and mTOR signaling impact peripheral T cell activation and fate. The contribution of mTOR and metabolism during early T-cell development in the thymus is also emerging and is the subject of this review. Two major T lineages with distinct immune functions and peripheral homing organs diverge during early thymic development; the αβ- and γδ-T cells, which are defined by their respective TCR subunits. Thymic T-regulatory cells, which have immunosuppressive functions, also develop in the thymus from positively selected αβ-T cells. Here, we review recent findings on how the two mTOR protein complexes, mTORC1 and mTORC2, and the signaling molecules involved in the mTOR pathway are involved in thymocyte differentiation. We discuss emerging views on how metabolic remodeling impacts early T cell development and how this can be mediated via mTOR signaling.
雷帕霉素的靶蛋白（mTOR）通过其在调节代谢中的功能来控制细胞命运和反应。雷帕霉素的免疫抑制特性的早期研究揭示了 mTOR 在控制免疫中的作用。最近的研究提供了关于代谢重编程和 mTOR 信号如何影响外周 T 细胞激活和命运的见解。mTOR 和代谢在胸腺中早期 T 细胞发育中的作用也在出现，这是本综述的主题。在早期胸腺发育过程中，具有不同免疫功能和外周归巢器官的两个主要 T 细胞谱系发生分歧；αβ-T 细胞和 γδ-T 细胞，它们分别由各自的 TCR 亚基定义。具有免疫抑制功能的胸腺 T 调节细胞也从阳性选择的 αβ-T 细胞中在胸腺中发育。在这里，我们综述了最近关于 mTOR 的两个蛋白复合物（mTORC1 和 mTORC2）以及参与 mTOR 途径的信号分子如何参与胸腺细胞分化的发现。我们讨论了代谢重塑如何影响早期 T 细胞发育以及如何通过 mTOR 信号介导的新观点。
