CD4 ⁺ Regulatory T Cells Control T _H 17 Responses in a Stat3-Dependent Manner

TLDR

Protective immunity is directed by STAT transcription factors, and CD4+ regulatory T cells suppress excessive responses, with deficiency causing lethal multi‑organ autoimmunity dominated by TH1 and TH2 lesions. We demonstrate that Tregs restrain pathogenic TH17 responses, a suppression that is lost when Tregs lack Stat3, resulting in fatal intestinal inflammation and revealing that Tregs adapt by engaging distinct STAT‑dependent suppression modalities.

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 (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.