Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom; email:
Annu Rev Immunol. 2018 Apr 26;36:411-433. doi: 10.1146/annurev-immunol-042617-053352.
The discovery of interleukin-2 (IL-2) changed the molecular understanding of how the immune system is controlled. IL-2 is a pleiotropic cytokine, and dissecting the signaling pathways that allow IL-2 to control the differentiation and homeostasis of both pro- and anti-inflammatory T cells is fundamental to determining the molecular details of immune regulation. The IL-2 receptor couples to JAK tyrosine kinases and activates the STAT5 transcription factors. However, IL-2 does much more than control transcriptional programs; it is a key regulator of T cell metabolic programs. The development of global phosphoproteomic approaches has expanded the understanding of IL-2 signaling further, revealing the diversity of phosphoproteins that may be influenced by IL-2 in T cells. However, it is increasingly clear that within each T cell subset, IL-2 will signal within a framework of other signal transduction networks that together will shape the transcriptional and metabolic programs that determine T cell fate.
白细胞介素-2(IL-2)的发现改变了人们对免疫系统如何受到控制的分子理解。IL-2 是一种多效细胞因子,解析允许 IL-2 控制促炎和抗炎 T 细胞分化和稳态的信号通路,对于确定免疫调节的分子细节至关重要。IL-2 受体与 JAK 酪氨酸激酶结合并激活 STAT5 转录因子。然而,IL-2 的作用远不止控制转录程序;它还是 T 细胞代谢程序的关键调节剂。全磷酸化蛋白质组学方法的发展进一步扩展了对 IL-2 信号的理解,揭示了 IL-2 可能在 T 细胞中影响的磷酸化蛋白的多样性。然而,越来越明显的是,在每个 T 细胞亚群中,IL-2 将在其他信号转导网络的框架内发出信号,这些网络共同将决定 T 细胞命运的转录和代谢程序塑造出来。
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