Cited by 839T-cell and B-cell ImmunologySignaling Pathways in DiseaseTGF-β signaling in diseases

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Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer

Tone, Yukiko, Furuuchi, Keiji, Kojima, Yoshitsugu, Tykocinski, Mark L, Greene, Mark I, Tone, Masahide·2008·Nature Immunology

DOI 10.1038/ni1549

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Abstract

The transcription factor Foxp3 is involved in the differentiation, function and survival of CD4+CD25+ regulatory T (T(reg)) cells. Details of the mechanism underlying the induction of Foxp3 expression remain unknown, because studies of the transcriptional regulation of the Foxp3 gene are limited by the small number of T(reg) cells in mononuclear cell populations. Here we have generated a model system for analyzing Foxp3 induction and, by using this system with primary T cells, we have identified an enhancer element in this gene. The transcription factors Smad3 and NFAT are required for activity of this Foxp3 enhancer, and both factors are essential for histone acetylation in the enhancer region and induction of Foxp3. These biochemical properties that define Foxp3 expression explain many of the effects of transforming growth factor-beta on the function of Foxp3+ T(reg) cells.

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Authors: Tone, Y., Furuuchi, K., Kojima, Y., Tykocinski, M. L., Greene, M. I., & Tone, M.
Affiliations: University of Pennsylvania (US)
Corresponding author: Tone, Masahide
ORCID: Furuuchi, Keiji
Kojima, Yoshitsugu
Tykocinski, Mark L
Greene, Mark I
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2007-12-23
Volume: 9
Issue: 2
Pages: 194-202
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1549
OpenAlex: W2019077533
Cited by: 807
References: 31
Citations by year: 2026: 16 · 2025: 17 · 2024: 32 · 2023: 34 · 2022: 35 · 2021: 41 · 2020: 45 · 2019: 49 · 2018: 44 · 2017: 45 · 2016: 47 · 2015: 54 · 2014: 45 · 2013: 64 · 2012: 37
FWCI: 17.12
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: Foxp3, regulatory T cells, Smad3, NFAT, transcriptional regulation, histone acetylation, TGF-beta, CD4+CD25+ T cells, transcription factor cooperation
MeSH terms: Animals, Base Sequence, Enhancer Elements, Genetic, Gene Expression Regulation, Molecular Sequence Data, Cell Line, Tumor, T-Lymphocytes, Regulatory, NFATC Transcription Factors, Mice, Forkhead Transcription Factors, Smad3 Protein

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Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer

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