Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Sci Signal. 2018 Apr 17;11(526):eaap8112. doi: 10.1126/scisignal.aap8112.
Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to promote the differentiation of effector CD8 cytotoxic T lymphocytes (CTLs). Using high-resolution mass spectrometry, we generated an in-depth characterization of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2 signaling through JAK1 and JAK3 (JAK1/3) increased the abundance of a key subset of proteins to induce the accumulation of critical cytokines and effector molecules in T cells. Moreover, IL-2 maintained the concentration of proteins that support core metabolic processes essential for cellular fitness. One fundamental insight was the dominant role for IL-2 in stimulating effector T cells to detect microenvironmental cues. IL-2-JAK1/3 signaling pathways thus increased the abundance of nutrient transporters, nutrient sensors, and critical oxygen-sensing molecules. These data provide key insights into how IL-2 promotes T cell function and highlight signaling mechanisms and transcription factors that integrate oxygen sensing to transcriptional control of CD8 T cell differentiation.
白细胞介素-2 (IL-2) 和 Janus 激酶 (JAK) 调节转录程序和蛋白质合成，以促进效应 CD8 细胞毒性 T 淋巴细胞 (CTL) 的分化。我们使用高分辨率质谱法，深入分析了 IL-2 和 JAK 如何构建 CTL 蛋白质组以控制 CTL 功能。我们发现，IL-2 通过 JAK1 和 JAK3 (JAK1/3) 信号转导增加了一组关键蛋白质的丰度，从而诱导 T 细胞中关键细胞因子和效应分子的积累。此外，IL-2 维持了支持细胞适应性所必需的核心代谢过程的蛋白质浓度。一个基本的认识是，IL-2 在刺激效应 T 细胞检测微环境信号方面起着主导作用。IL-2-JAK1/3 信号通路因此增加了营养转运蛋白、营养传感器和关键的氧感应分子的丰度。这些数据为 IL-2 如何促进 T 细胞功能提供了重要的见解，并强调了信号转导机制和转录因子，它们将氧感应整合到 CD8 T 细胞分化的转录控制中。
