Bach2 attenuates IL-2R signaling to control Treg homeostasis and Tfr development

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. [Display omitted] •Bach2 suppresses CD25/IL-2R signaling in Tregs•Enhanced IL-2R signaling counteracts the poor survival of Bach2-deficient rTregs•Bach2 promotes the development of highly differentiated Tfr cells•Treg-specific ablation of Bach2 provokes late-onset autoimmunity Transcriptional control of various Treg subtypes remains incompletely understood. Zhang et al. report that the transcription factor Bach2 is required for the maintenance of resting Treg cells and promotes full differentiation of a germinal-center-resident Tfr subset to prevent autoimmunity