Tissue Regulatory T Cells

FOXP3+ regulatory T cells (Tregs) have well-defined roles in limiting systemic immune responses against diverse stimuli. However, the observation that a subset of Tregs also enter nonlymphoid tissues, where they assume additional functions, has become increasingly apparent. These tissue-resident Tregs have diverse beneficial roles in tissue physiology, such as aiding homeostasis and promoting tissue repair and regeneration. In this article, we survey the state of knowledge of tissue Treg form and function in fat, muscle, heart, brain, skin, lung, and gut tissue. From a synthesis of the broader scope of the molecular features and cellular kinetics emerges a converging program of tissue residency shared across tissues and species. A core residency module drives tissue residency for Tregs, with a dynamic cellular flux of tissue-resident cells during homeostasis and disease. Finally, we review the potential for clinical translation and the key unknowns to address for the therapeutic exploitation of this enigmatic population.