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Science 326 (5955): 986-991

Copyright © 2009 by the American Association for the Advancement of Science

CD4+ Regulatory T Cells Control TH17 Responses in a Stat3-Dependent Manner

Ashutosh Chaudhry,1,2 Dipayan Rudra,1,2 Piper Treuting,3 Robert M. Samstein,1 Yuqiong Liang,1 Arnold Kas,2 Alexander Y. Rudensky1,2,*

Abstract: Distinct classes of protective immunity are guided by activation of STAT transcription factor family members in response to environmental cues. CD4+ regulatory T cells (Tregs) suppress excessive immune responses, and their deficiency results in a lethal, multi-organ autoimmune syndrome characterized by T helper 1 (TH1) and T helper 2 (TH2) CD4+ T cell–dominated lesions. Here we show that pathogenic TH17 responses in mice are also restrained by Tregs. This suppression was lost upon Treg-specific ablation of Stat3, a transcription factor critical for TH17 differentiation, and resulted in the development of a fatal intestinal inflammation. These findings suggest that Tregs adapt to their environment by engaging distinct effector response–specific suppression modalities upon activation of STAT proteins that direct the corresponding class of the immune response.

1 Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2 Department of Immunology, University of Washington, Seattle, WA 98195, USA.
3 Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.

* To whom correspondence should be addressed. E-mail: rudenska{at}

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