Cited by 1,982T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisTGF-β signaling in diseases

Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid

Mucida, Daniel, Park, Yunji, Kim, Gisen, Turovskaya, Olga, Scott, Iain, Kronenberg, Mitchell, Cheroutre, Hilde·2007·Science

Abstract

The cytokine transforming growth factor–β (TGF-β) converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-β has also been found to promote the differentiation of naïve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (T H 17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-β can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-β–dependent immune responses, capable of inhibiting the IL-6–driven induction of proinflammatory T H 17 cells and promoting anti-inflammatory Treg cell differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity.

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Crossref · 10.1126/science.1145697

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Authors
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H.
Affiliations
La Jolla Institute for Immunology (US)
Corresponding author
Cheroutre, Hilde
Venue
Science
Published
2007-07-13
Volume
317
Issue
5835
Pages
256-260
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2037259928
Cited by
1,982
References
17
Citations by year
2026: 43 · 2025: 60 · 2024: 54 · 2023: 68 · 2022: 77 · 2021: 73 · 2020: 86 · 2019: 76 · 2018: 82 · 2017: 81 · 2016: 92 · 2015: 136 · 2014: 113 · 2013: 143 · 2012: 123
FWCI
63.50
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai050265-13)
  • National Institute of Allergy and Infectious Diseases (R01 AI050265-06)
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 › TGF-β signaling in diseases
Keywords
retinoic acid, TGF-beta, Th17 cells, regulatory T cells, interleukin-6, naive T cell differentiation, vitamin A metabolites, autoimmunity, inflammation
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Colitis, Dendritic Cells, Dibenzazepines, T-Lymphocytes, Helper-Inducer, Interleukin-2, Intestinal Mucosa, Listeriosis, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Spleen, Tretinoin, Interleukin-6, T-Lymphocyte Subsets, Transforming Growth Factor beta, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors

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