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

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 (T(H)1) and T helper 2 (T(H)2) CD4(+) T cell-dominated lesions. Here we show that pathogenic T(H)17 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 T(H)17 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.