Abstract
Recent studies have demonstrated that plasticity of naturally occurring CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to control chronic inflammation in established autoimmune diseases. All-trans retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated to promote Foxp3(+) Treg differentiation and suppress Th17 development. In this study, we report a vital role of atRA in sustaining the stability and functionality of nTregs in the presence of IL-6. We found that nTregs treated with atRA were resistant to Th17 and other Th cell conversion and maintained Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA decreased IL-6R expression and signaling by nTregs. Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppressed progression of established collagen-induced arthritis. We suggest that nTregs treated with atRA may represent a novel treatment strategy to control established chronic immune-mediated inflammatory diseases.
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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Arthritis, Experimental / immunology*
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Arthritis, Experimental / metabolism
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Arthritis, Experimental / pathology*
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / metabolism
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Autoimmune Diseases / pathology*
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Cells, Cultured
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Female
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Forkhead Transcription Factors / biosynthesis
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Gene Knock-In Techniques
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Immunity, Innate / genetics
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Immunophenotyping
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Inflammation Mediators / pharmacology
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Inflammation Mediators / physiology*
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Interleukin-17 / biosynthesis
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Interleukin-6 / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / pathology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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Tretinoin / pharmacology
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Tretinoin / physiology*
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Inflammation Mediators
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Interleukin-17
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Interleukin-6
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Tretinoin