Robust and effective T cell-mediated immune responses require proper allocation of metabolic resources through metabolic pathways to sustain the energetically costly immune response. As an essential class of polycationic metabolites ubiquitously present in all living organisms, the polyamine pool is tightly regulated by biosynthesis and salvage pathway. We demonstrated that arginine is a major carbon donor and glutamine is a minor carbon donor for polyamine biosynthesis in T cells. Accordingly, the dependence of T cells can be partially relieved by replenishing the polyamine pool. In response to the blockage of de novo synthesis, T cells can rapidly restore the polyamine pool through a compensatory increase in polyamine uptake from the environment, indicating a layer of metabolic plasticity. Simultaneously blocking synthesis and uptake depletes the intracellular PA pool, inhibits T cell proliferation, suppresses T cell inflammation, indicating the potential therapeutic value of targeting the polyamine for managing inflammatory and autoimmune diseases.

中文翻译：

---

从头合成和挽救途径协调调节多胺稳态并决定T细胞增殖和功能

强大且有效的T细胞介导的免疫反应需要通过代谢途径适当分配代谢资源，以维持能量上昂贵的免疫反应。作为所有生命有机体中普遍存在的一类重要的聚阳离子代谢产物，多胺库受到生物合成和挽救途径的严格调控。我们证明精氨酸是主要的碳供体，而谷氨酰胺是次要的碳供体，用于T细胞中多胺的生物合成。因此，通过补充多胺池可以部分减轻T细胞的依赖性。响应于从头合成的阻滞，T细胞可通过补偿性增加环境中多胺的摄取来迅速恢复多胺库，表明有一层代谢可塑性。