IL‐27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1

Abstract

IL‐27 is an IL‐12‐related cytokine frequently present at sites of inflammation that can promote both anti‐ and pro‐inflammatory immune responses. Here, we have analyzed the mechanisms how IL‐27 may drive such divergent immune responses. While IL‐27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti‐inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL‐27 suppressed the development of adaptive, TGF‐β‐induced Forkhead box transcription factor p3‐positive (Foxp3⁺) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg development was STAT1 independent, suggesting that IL‐27 utilizes different signaling pathways to shape T cell‐driven immune responses. Our data thus demonstrate that IL‐27 controls the development of Th17 and iTreg cells via differential effects on STAT1.