The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells

The local environment may affect the development and function of tissue-resident T regulatory cells (Tregs), which are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Tregs (pTregs) in the gut and that its expression was independent of microbiota. Ahr was important for Treg gut homing and function. Ahr inhibited pro-inflammatory cytokines produced by Tregs but was dispensable for Treg stability. Furthermore, Ahr-expressing Tregs had enhanced in vivo suppressive activity compared with Tregs lacking Ahr expression in a T cell transfer model of colitis. Our data suggest that Ahr signaling in Tregs may be important for gut immune homeostasis. [Display omitted] •Ahr is preferentially expressed by intestinal pTregs independent of the microbiota•Ahr regulates Treg homing to the gut•Ahr is important for in vivo Treg function but not Foxp3 expression•Ahr-expressing Tregs have enhanced suppressive activity in a model of colitis Ye et al. find that Ahr is most abundantly expressed by peripherally derived Tregs (pTregs) in the gut. Ahr expression and activation are important for Treg gut homing and function to suppress intestinal inflammation.