BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology

Achia Khatun, Xiaopeng Wu, Fu Qi, Kexin Gai, Arjun Kharel, Matthew R. Kudek, Lisa Fraser, Ashley Ceicko, Moujtaba Y. Kasmani, Amber Majnik, Robert Burns, Yi Guang Chen, Nita Salzman, Elizabeth J. Taparowsky, Dayu Fang, Calvin B. Williams*, Weiguo Cui*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuous T cell receptor (TCR) signaling plays a vital role in the differentiation of aTregs from their resting state, and in their immune homeostasis. The process by which Tregs differentiate, adapt tissue specificity, and maintain stable phenotypic expression at the transcriptional level is still inconclusivei. In this work, the role of BATF is investigated, which is induced in response to TCR stimulation in naïve T cells and during aTreg differentiation. Mice lacking BATF in Tregs developed multiorgan autoimmune pathology. As a transcriptional regulator, BATF is required for Treg differentiation, homeostasis, and stabilization of FOXP3 expression in different lymphoid and non-lymphoid tissues. Epigenetically, BATF showed direct regulation of Treg-specific genes involved in differentiation, maturation, and tissue accumulation. Most importantly, FOXP3 expression and Treg stability require continuous BATF expression in Tregs, as it regulates demethylation and accessibility of the CNS2 region of the Foxp3 locus. Considering its role in Treg stability, BATF should be considered an important therapeutic target in autoimmune disease.

Original languageEnglish (US)
Article number2206692
JournalAdvanced Science
Volume10
Issue number28
DOIs
StatePublished - Oct 6 2023

Keywords

  • BATF
  • Foxp3
  • Treg
  • autoimmunity

ASJC Scopus subject areas

  • General Engineering
  • General Chemical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Materials Science
  • General Physics and Astronomy
  • Medicine (miscellaneous)

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