Cited by 807T-cell and B-cell ImmunologySignaling Pathways in DiseaseTGF-β signaling in diseases

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

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.

Integrity signals

Registry

Crossref · 10.1038/ni1549

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In naïve CD4+ T cells, TGF-β/Smad3 signaling activates Foxp3, which encodes a master transcription factor that directs differentiation into activated CD4+Foxp3+CD25+ Treg cells.

    “In naïve CD4+ T cells, TGF-β/Smad3 signaling activates Foxp3, which encodes a master transcription factor that directs differentiation into activated CD4+Foxp3+CD25+ Treg cells60.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [60]

  • TGF-β in the presence of IL-2 promotes functional differentiation and survival of CD4+ Treg cells.

    “Importantly, TGF-β in the presence of IL-2 promotes functional differentiation and survival of CD4+ Treg cells.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [60]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Tone, Y., Furuuchi, K., Kojima, Y., Tykocinski, M. L., Greene, M. I., & Tone, M.
Affiliations
University of Pennsylvania (US)
Corresponding author
Tone, Masahide
Venue
Nature Immunology
Published
2007-12-23
Volume
9
Issue
2
Pages
194-202
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review