Chapman Nicole M, Chi Hongbo
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Immunotherapy. 2014;6(12):1295-311. doi: 10.2217/imt.14.84.
Foxp3(+) Tregs are central regulators of immune tolerance. As dysregulated Treg responses contribute to disease pathogenesis, novel approaches to target the immunomodulatory functions of Tregs are currently under investigation. mTORC1 and mTORC2 are therapeutic targets of interest. Recent studies revealed that mTOR signaling impacts conventional T-cell homeostasis, activation and differentiation. Moreover, mTOR controls the differentiation and functions of Tregs, suggesting that its activity could be targeted to modulate Treg responses. Here, we summarize how Tregs suppress immune responses, their roles in disease development and methods used to alter their functions therapeutically. We also discuss the diverse effects exerted by mTOR inhibition on the development, homeostasis, and functions of conventional T cells and Tregs. We conclude with a discussion of how modulation of mTOR activity in Tregs may be therapeutically beneficial or detrimental in different disease settings.
Foxp3(+)调节性T细胞是免疫耐受的核心调节因子。由于调节性T细胞反应失调会导致疾病发病机制，目前正在研究针对调节性T细胞免疫调节功能的新方法。哺乳动物雷帕霉素靶蛋白复合体1（mTORC1）和哺乳动物雷帕霉素靶蛋白复合体2（mTORC2）是备受关注的治疗靶点。最近的研究表明，mTOR信号传导影响传统T细胞的稳态、激活和分化。此外，mTOR控制调节性T细胞的分化和功能，这表明其活性可作为调节调节性T细胞反应的靶点。在此，我们总结了调节性T细胞如何抑制免疫反应、它们在疾病发展中的作用以及用于治疗性改变其功能的方法。我们还讨论了mTOR抑制对传统T细胞和调节性T细胞的发育、稳态及功能产生的多种影响。我们最后讨论了在不同疾病背景下，调节调节性T细胞中的mTOR活性在治疗上可能有益或有害的情况。
