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

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.

Keywords: Bach2; CD25; IL-2R signaling; Tfr; Treg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Differentiation
  • Homeostasis
  • Interleukin-2 / metabolism*
  • Mice
  • Receptors, Transferrin / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / metabolism*


  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Interleukin-2
  • Receptors, Transferrin
  • Tfrc protein, mouse