Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4

Preston R. Arnold, Mou Wen, Lei Zhang, Yuanlin Ying, Xiang Xiao, Xiufeng Chu, Guangchuan Wang, Xiaolong Zhang, Zhuyun Mao, Aijun Zhang, Dale J. Hamilton, Wenhao Chen, Xian C. Li

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. We found that IRF4 must partner with BATF3 to bind to a regulatory region in the Foxp3 locus where they cooperatively repress FOXP3 expression and iTreg induction. In addition, we found that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. As a result, Irf4 KO iTregs show increased demethylation of the critical CNS2 region in the Foxp3 locus. Together, our findings provide important insights how BATF3 and IRF4 interactions integrate activating signals to control CD4+ cell fate decisions and govern Foxp3 expression.

Original languageEnglish (US)
Article number966364
Pages (from-to)966364
JournalFrontiers in immunology
StatePublished - Aug 25 2022


  • BATF family
  • cell fate decision
  • Foxp3
  • glycolytic reprogramming
  • IRF4
  • regulatory T (Treg) cell
  • super enhancer
  • TCR signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4'. Together they form a unique fingerprint.

Cite this