Shanghai Institute of Immunology & Department of Immunology and Microbiology, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Cell Rep. 2021 May 11;35(6):109096. doi: 10.1016/j.celrep.2021.109096.
Differentiation and homeostasis of Foxp3 regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here, we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis. Bach2 is required for the quiescence, survival, and maintenance of resting Treg cells (rTregs). Unexpectedly, Bach2 directly represses CD25 (IL-2Rα) and subsequently attenuates IL-2R signaling in Tregs. Upregulated CD25/IL-2R signaling in Bach2-deficient rTregs acts as a parallel pathway to partially counteract their poor survival and maintenance. Furthermore, Bach2 suppresses CD25/IL-2R signaling in T follicular regulatory (Tfr) cells. Bach2 deficiency in Tregs prevents the formation of highly differentiated Tfr cells, associated with aberrant GC response. Finally, a mild and late onset of autoimmune disease is observed in mice with Bach2-deficient Tregs. Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.
叉头框蛋白 P3（Foxp3）调节性 T 细胞（Tregs）的分化和稳态受白细胞介素 2 受体（IL-2R）信号的严格控制，但这些过程的调控机制尚不完全清楚。在这里，我们报告转录因子 Bach2 可减弱 IL-2R 信号，以协调 Treg 的分化和稳态。Bach2 对于静止、存活和维持静息 Treg 细胞（rTregs）是必需的。出乎意料的是，Bach2 可直接抑制 CD25（IL-2Rα），从而减弱 Tregs 中的 IL-2R 信号。Bach2 缺陷型 rTregs 中上调的 CD25/IL-2R 信号可作为平行途径，部分抵消其存活和维持不良的情况。此外，Bach2 可抑制滤泡辅助性 T 细胞（Tfh）中的 CD25/IL-2R 信号。Tregs 中的 Bach2 缺陷可防止高度分化的 Tfh 细胞的形成，与异常 GC 反应有关。最后，在 Bach2 缺陷型 Tregs 小鼠中观察到自身免疫疾病的轻度和迟发性发作。因此，Bach2 可平衡 IL-2R 信号，以协调各种 Treg 亚群的发育和稳态。
