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

Heng Zhang; Di Dai; Qianwen Hu; Fang Yang; Yishu Xue; Fubin Li; Nan Shen; Min Zhang; Chuanxin Huang

doi:10.1016/j.celrep.2021.109096

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.

Authors

Heng Zhang¹, Di Dai¹, Qianwen Hu¹, Fang Yang¹, Yishu Xue², Fubin Li¹, Nan Shen³, Min Zhang⁴, Chuanxin Huang⁵

Affiliations

¹ Shanghai Institute of Immunology & Department of Immunology and Microbiology, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
³ Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China.
⁴ Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: 13482345145@163.com.
⁵ Shanghai Institute of Immunology & Department of Immunology and Microbiology, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: huangcx@shsmu.edu.cn.

PMID: 33979619
DOI: 10.1016/j.celrep.2021.109096

Abstract

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*

Substances

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