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-2R alpha) 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.