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Science. 2009 Nov 13;326(5955):986-91. doi: 10.1126/science.1172702. Epub 2009 Oct 1.

CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.

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Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.


Distinct classes of protective immunity are guided by activation of STAT transcription factor family members in response to environmental cues. CD4+ regulatory T cells (T(regs)) 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 T(regs). This suppression was lost upon T(reg)-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 T(regs) 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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