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Published Online June 14, 2007
Science DOI: 10.1126/science.1145697

Reports

Submitted on February 22, 2007
Accepted on June 6, 2007

Reciprocal Th-17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid

Daniel Mucida 1, Yunji Park 1, Gisen Kim 1, Olga Turovskaya 1, Iain Scott 1, Mitchell Kronenberg 1, Hilde Cheroutre 1

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

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 (IL)-6, TGF-{beta} has also been found to promote differentiation of naïve T lymphocytes into pro-inflammatory IL-17 cytokine-producing T helper 17 (Th-17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-{beta} can generate such distinct outcomes. Here we identified the vitamin A metabolite, retinoic acid (RA), as a key regulator of TGF-{beta}-dependent immune responses, capable of inhibiting the IL-6-driven induction of pro-inflammatory Th-17 cells and promoting anti-inflammatory Treg differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity.


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