Abstract
The cytokine transforming growth factor-beta (TGF-beta) converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-beta 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-beta can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-beta-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cells, Cultured
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Colitis / immunology
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Dendritic Cells / immunology
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Dibenzazepines / pharmacology
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Forkhead Transcription Factors / biosynthesis
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Interleukin-17 / biosynthesis*
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Interleukin-2 / immunology
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Interleukin-6 / immunology
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology
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Listeriosis / immunology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / pharmacology
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Tretinoin / pharmacology
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Tretinoin / physiology*
Substances
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Dibenzazepines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Interleukin-17
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Interleukin-2
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Interleukin-6
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LE 540
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Transforming Growth Factor beta
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Tretinoin