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Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Abstract
CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. Here we report that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development. The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic defect of CD4+CD25- T cells. CD4+CD25+ regulatory T cells rescue disease development and preferentially expand when transferred into neonatal Foxp3-deficient mice. Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25- T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function.
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“Beneficial Treg cell functions are apparent in the uncontrolled inflammation and fatal tissue damage observed in Foxp3 -/- mice 20,21 , a phenotype that can be rescued by transfer of T cells expressing Foxp3 20,21 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [20]
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Metadata
- Authors
- Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rudensky, Alexander Y.
- Venue
- Nature Immunology
- Published
- 2003-03-03
- Volume
- 4
- Issue
- 4
- Pages
- 330-336
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2097811455
- Cited by
- 7,745
- References
- 26
- Citations by year
- 2026: 168 · 2025: 199 · 2024: 237 · 2023: 230 · 2022: 306 · 2021: 323 · 2020: 326 · 2019: 318 · 2018: 287 · 2017: 307 · 2016: 296 · 2015: 303 · 2014: 351 · 2013: 392 · 2012: 414
- FWCI
- 106.35
- 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 › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- Foxp3, regulatory T cells, CD4+CD25+ T cells, Treg development, autoimmunity, scurfy mice, Treg suppressive function, transcription factors
- MeSH terms
- Animals, DNA-Binding Proteins, Female, Receptors, Interleukin-2, CD4-Positive T-Lymphocytes, Down-Regulation, Gene Targeting, Mice, Forkhead Transcription Factors
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