The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20080034
The Journal of Experimental Medicine, Vol. 205, No. 6, 1381-1393
The Rockefeller University Press, 0022-1007 $30.00
© Lochner et al.
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ARTICLE

 In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ ROR{gamma}t+ T cells

Matthias Lochner1, Lucie Peduto1, Marie Cherrier1, Shinichiro Sawa1, Francina Langa2, Rosa Varona5, Dieter Riethmacher6, Mustapha Si-Tahar3, James P. Di Santo4, and Gérard Eberl1

1 Laboratory of Lymphoid Tissue Development, Centre National de la Recherche Scientifique (CNRS) URA1961, 2 Centre Ingéniérie Génétique Murine, 3 Unité de Défense Innée et Inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM) U874, and 4 Unité des Cytokines et Développement Lymphoïde, INSERM U668, Institut Pasteur, Paris 75724, France
5 Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, UAM Campus Cantoblanco, Madrid 28049, Spain
6 Development and Regeneration, Human Genetics Division, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK

CORRESPONDENCE Gérard Eberl: geberl{at}pasteur.fr

The nuclear hormone receptor retinoic acid receptor–related orphan receptor {gamma}t (ROR{gamma}t) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of ROR{gamma}t+ T cells express IL-17. We report here that ROR{gamma}t+ T{alpha}β cells include Foxp3+ cells that coexist with IL-17–producing ROR{gamma}t+ T{alpha}β cells in all tissues examined. The Foxp3+ ROR{gamma}t+ T{alpha}β express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3+ to IL-17–producing ROR{gamma}t+ T{alpha}β cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of ROR{gamma}t+ T cells express the {gamma}{delta} T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17–producing and regulatory Foxp3+ ROR{gamma}t+ T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in ROR{gamma}t+ T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.

Abbreviations used: BAC, bacterial artificial chromosome; CIA, collagen-induced arthritis; DSS, dextran sodium sulfate; EGFP, enhanced GFP; LTi, lymphoid tissue inducer; RA, retinoic acid; ROR{gamma}t, RA receptor–related orphan receptor {gamma}t; T reg, T regulatory.

L. Peduto and M. Cherrier contributed equally to this work.

© 2008 Lochner et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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