Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
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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RA inhibited IL-6-driven induction of proinflammatory Th17 cells and promoted the differentiation of Treg cells.
“RA inhibited IL-6-driven induction of proinflammatory Th17 cells and promoted the differentiation of Treg cells, which are important to suppress excessive immune responses125.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [125]
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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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