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

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Science  13 Nov 2009:
Vol. 326, Issue 5955, pp. 986-991
DOI: 10.1126/science.1172702

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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.

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