Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States.
Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2018 Jan 29;9:69. doi: 10.3389/fimmu.2018.00069. eCollection 2018.
CD4 Foxp3 regulatory T cells (Tregs) are an essential component of immune homeostasis. Modulation of Treg function has been proposed as a means of treating autoimmune conditions and preventing rejection of organ transplants, although achieving this goal will require a detailed understanding of Treg signaling pathways. Signaling within Tregs is known to differ considerably from that observed in other T cell subsets. Of note, Tregs are the only cell type known to constitutively express CD25, the main ligand-binding subunit of the IL-2 receptor. The PI(3)K/Akt/mTOR cascade constitutes a major signaling pathway downstream of IL-2 and is closely tied to cellular metabolism. Due to increasing recognition of the links between cellular fuel usage and immune cell function, the interplay between IL-2 signaling and Treg metabolism represents an important space for exploration and a potential approach for immunomodulation. Here, we discuss how IL-2 may affect Treg metabolism PI(3)K signaling, as well as the effects of altered metabolism on Treg lineage stability and suppressor function.
CD4+Foxp3+ 调节性 T 细胞（Tregs）是免疫稳态的重要组成部分。调节 Treg 功能已被提议作为治疗自身免疫性疾病和防止器官移植排斥的一种手段，尽管要实现这一目标，还需要详细了解 Treg 信号通路。众所周知，Tregs 内的信号转导与其他 T 细胞亚群观察到的信号转导有很大的不同。值得注意的是，Tregs 是唯一已知持续表达 IL-2 受体主要配体结合亚基 CD25 的细胞类型。PI(3)K/Akt/mTOR 级联反应是 IL-2 下游的主要信号通路，与细胞代谢密切相关。由于越来越多的人认识到细胞燃料利用与免疫细胞功能之间的联系，IL-2 信号与 Treg 代谢之间的相互作用代表了一个值得探索的重要领域，也是一种潜在的免疫调节方法。在这里，我们讨论了 IL-2 如何影响 Treg 代谢和 PI(3)K 信号，以及代谢改变对 Treg 谱系稳定性和抑制功能的影响。
