Induction and maintenance of regulatory T cells by transcription factors and epigenetic modifications

Mana Iizuka-Koga, Hiroko Nakatsukasa, Minako Ito, Takashi Akanuma, Qianjin Lu, Akihiko Yoshimura

Research output: Contribution to journalReview articlepeer-review

52 Citations (Scopus)


Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3. Several intronic enhancers and a promoter at the Foxp3 gene locus were shown to play important roles in Treg differentiation. The enhancers have been designated as conserved non-coding sequences (CNSs) 0, 1, 2, and 3. We showed that the transcription factors Nr4a and Smad2/3 are essential for the development of thymic Tregs and induced Tregs, respectively. Recently, Treg-specific DNA demethylation has been shown to play an important role in Treg stability. DNA demethylation of CNS2 has been implicated in Treg stability, and recent reports have revealed that the ten-eleven translocation (Tet) family of demethylation factor plays an important role in CpG demethylation at CNS2. This article reviews the recent progress on the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalJournal of Autoimmunity
Publication statusPublished - 2017 Sept


  • DNA methylation
  • Epigenetics
  • Foxp3
  • Nr4a
  • Regulatory T cell
  • Smad
  • TGF-β
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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