Adaptive immunity is essential for pathogen and tumor eradication, but may also trigger uncontrolled or pathological inflammation. T cell receptor, co-stimulatory and cytokine signals coordinately dictate specific signaling networks that trigger the activation and functional programming of T cells. In addition, cellular metabolism promotes T cell responses and is dynamically regulated through the interplay of serine/threonine kinases, immunological cues and nutrient signaling networks. In this review, we summarize the upstream regulators and signaling effectors of key serine/threonine kinase-mediated signaling networks, including PI3K–AGC kinases, mTOR and LKB1–AMPK pathways that regulate metabolism, especially in T cells. We also provide our perspectives about the pending questions and clinical applicability of immunometabolic signaling. Understanding the regulators and effectors of immunometabolic signaling networks may uncover therapeutic targets to modulate metabolic programming and T cell responses in human disease.

适应性免疫对于根除病原体和肿瘤至关重要，但也可能引发不受控制或病理性炎症。T 细胞受体、共刺激和细胞因子信号协调决定触发 T 细胞激活和功能编程的特定信号网络。此外，细胞代谢促进 T 细胞反应，并通过丝氨酸/苏氨酸激酶、免疫信号和营养信号网络的相互作用进行动态调节。在这篇综述中，我们总结了关键丝氨酸/苏氨酸激酶介导的信号网络的上游调节因子和信号效应因子，包括调节代谢的 PI3K-AGC 激酶、mTOR 和 LKB1-AMPK 通路，尤其是在 T 细胞中。我们还提供了关于免疫代谢信号传导的悬而未决问题和临床适用性的观点。