TY - JOUR
T1 - Induction and maintenance of regulatory T cells by transcription factors and epigenetic modifications
AU - Iizuka-Koga, Mana
AU - Nakatsukasa, Hiroko
AU - Ito, Minako
AU - Akanuma, Takashi
AU - Lu, Qianjin
AU - Yoshimura, Akihiko
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant-in-Aid for Young Scientists (A) and (S) No. 25221305; Advanced Research & Development Programs for Medical Innovation (AMED-CREST); the Takeda Science Foundation; the Uehara Memorial Foundation; the Mochida Memorial Foundation for Medical and Pharmaceutical Research; the Kanae Foundation; the SENSHIN Medical Research Foundation; and Keio Gijuku Academic Developmental Funds.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Epigenetics
KW - Foxp3
KW - Nr4a
KW - Regulatory T cell
KW - Smad
KW - TGF-β
KW - Transcription factors
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U2 - 10.1016/j.jaut.2017.07.002
DO - 10.1016/j.jaut.2017.07.002
M3 - Review article
C2 - 28709726
AN - SCOPUS:85023169673
SN - 0896-8411
VL - 83
SP - 113
EP - 121
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -