Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid |
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Authors: | Mucida Daniel Park Yunji Kim Gisen Turovskaya Olga Scott Iain Kronenberg Mitchell Cheroutre Hilde |
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Affiliation: | La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. |
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Abstract: | The cytokine transforming growth factor-beta (TGF-beta) converts na?ve 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 na?ve 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. |
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