Institute of special environmental medicine, Nantong University, Nantong, 226019, China.
Geriatrics Department, Nantong First People's Hospital, Nantong 226001, Jiangsu, China.
Int Immunopharmacol. 2022 Jul;108:108823. doi: 10.1016/j.intimp.2022.108823. Epub 2022 May 25.
CD4Foxp3 regulatory T cells (Tregs), a subpopulation of CD4 T cells, are engaged in maintaining the periphery tolerance and preventing autoimmunity. Recent studies showed that tumor necrosis factor receptor 2 (TNFR2) is preferentially expressed by Tregs and the expression of this receptor identifies the maximally suppressive Tregs. That is, TNFR2 is a liable phenotypic and functional surface marker of Tregs. Moreover, TNF activates and expands Tregs through TNFR2. However, it is very interesting which signaling pathway(s) of TNFR2 is required for the inhibitory effect of Tregs. Compelling evidence shows three TNFR2 signaling pathways in Tregs, including NF-κB, MAPK and PI3K-Akt pathways. Here, we summarize and discuss the latest progress in the studies on the downstream signaling pathways of TNF-TNFR2 for controlling Treg homeostasis, differentiation and proliferation.
CD4Foxp3 调节性 T 细胞（Tregs）是 CD4 T 细胞的一个亚群，参与维持外周耐受和防止自身免疫。最近的研究表明，肿瘤坏死因子受体 2（TNFR2）优先在 Tregs 上表达，而该受体的表达鉴定了具有最大抑制作用的 Tregs。也就是说，TNFR2 是 Tregs 的一种易于表现和功能的表面标志物。此外，TNF 通过 TNFR2 激活和扩增 Tregs。然而，有趣的是，TNFR2 的哪种（些）信号通路对于 Tregs 的抑制作用是必需的。令人信服的证据表明，Tregs 中存在三种 TNFR2 信号通路，包括 NF-κB、MAPK 和 PI3K-Akt 通路。在这里，我们总结和讨论了关于 TNF-TNFR2 控制 Treg 动态平衡、分化和增殖的下游信号通路的最新研究进展。
