Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
J Cell Physiol. 2019 Aug;234(8):12353-12368. doi: 10.1002/jcp.28042. Epub 2019 Feb 2.
The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase-related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T-cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8 T-cells differentiation and homeostasis in a T-cell-intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 T-cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities.
哺乳动物雷帕霉素靶蛋白（mTOR）是进化磷脂酰肌醇激酶相关激酶（PIKKs）家族的成员。mTOR 在调节细胞生理的多个方面起着关键作用，如身体代谢、细胞生长、蛋白质合成、细胞大小、自噬和细胞分化。在免疫学方面，mTOR 对先天和适应性免疫细胞的多种功能的控制和塑造具有基本作用，特别是 T 细胞亚群的分化、存活和代谢重编程，最终调节多种免疫细胞类型的命运。研究人员报告称，雷帕霉素是一种选择性 mTOR 抑制剂和免疫抑制剂，它以 T 细胞内在的方式对诱导病毒特异性记忆 CD8 T 细胞分化和稳态的数量和质量方面具有惊人的免疫刺激作用。mTOR 信号通路在调节调节性 T 细胞（Treg）、辅助性 T 细胞 17（Th17）细胞和自然杀伤（NK）细胞增殖和成熟，以及 NK 细胞的效应功能和细胞毒性特性方面也起着关键作用。操纵 mTOR 活性是一种寻求抑制 mTOR 的药理学药物的关键治疗方法。这种方法应增强特定记忆 CD8 T 细胞的反应，并诱导 NK 细胞的完全功能性效应功能，以激发其抗肿瘤和抗病毒活性。
