CD4~+ Regulatory T Cells Control T_H17 Responses in a Stat3-Dependent Manner

摘要

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_H1) and T helper 2 (T_H2) CD4~+ T cell-dominated lesions. Here we show that pathogenic T_H17 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_H17 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.