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Originally published in Science Express on 14 June 2007
Science 13 July 2007:
Vol. 317. no. 5835, pp. 256 - 260
DOI: 10.1126/science.1145697
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Reports

Reciprocal TH17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid

Daniel Mucida, Yunji Park, Gisen Kim, Olga Turovskaya, Iain Scott, Mitchell Kronenberg, Hilde Cheroutre*

The cytokine transforming growth factor–ß (TGF-ß) converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-ß has also been found to promote the differentiation of naïve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (TH17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-ß can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-ß–dependent immune responses, capable of inhibiting the IL-6–driven induction of proinflammatory TH17 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.

La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: hilde{at}liai.org

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