Table_1_TNFR2 Costimulation Differentially Impacts Regulatory and Conventional CD4+ T-Cell Metabolism.xlsx

CD4+ conventional T cells (Tconvs) mediate adaptive immune responses, whereas regulatory T cells (Tregs) suppress those responses to safeguard the body from autoimmunity and inflammatory diseases. The opposing activities of Tconvs and Tregs depend on the stage of the immune response and their environment, with an orchestrating role for cytokine- and costimulatory receptors. Nutrient availability also impacts T-cell functionality via metabolic and biosynthetic processes that are largely unexplored. Many data argue that costimulation by Tumor Necrosis Factor Receptor 2 (TNFR2) favors support of Treg over Tconv responses and therefore TNFR2 is a key clinical target. Here, we review the pertinent literature on this topic and highlight the newly identified role of TNFR2 as a metabolic regulator for thymus-derived (t)Tregs. We present novel transcriptomic and metabolomic data that show the differential impact of TNFR2 on Tconv and tTreg gene expression and reveal distinct metabolic impact on both cell types.

CD4+常规T细胞（Tconvs）介导适应性免疫反应，而调节性T细胞（Tregs）则抑制这些反应以保护机体免受自身免疫和炎症性疾病的影响。Tconvs和Tregs的拮抗作用取决于免疫反应的阶段及其所处环境，其中细胞因子和共刺激受体扮演着协调者的角色。营养物质的可用性也通过代谢和生物合成过程影响T细胞的功能，这些过程在很大程度上尚未得到充分探索。众多数据表明，肿瘤坏死因子受体2（TNFR2）的共刺激有利于支持Treg而非Tconv反应，因此TNFR2是一个关键的临床靶点。在本研究中，我们回顾了与此主题相关的文献，并突出了TNFR2作为胸腺衍生（t）Tregs的代谢调节器的新发现作用。我们呈现了新的转录组和代谢组数据，这些数据揭示了TNFR2对Tconv和tTreg基因表达的差异性影响，并揭示了两种细胞类型在代谢上的独特影响。