Mucosal tissue regulatory T cells are integral in balancing immunity and tolerance at portals of antigen entry

Foxp3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that exert suppressive control over other immune cells. Tregs are critical for preventing systemic autoimmunity and maintaining peripheral tolerance, and yet they also assist in orchestration of immunity to pathogenic insult, wherein they limit collateral immunopathology and assist in facilitating a fine balance between immune tolerance and effector activity. Tregs have been extensively studied in lymphoid tissues, and a growing body of work has characterized phenotypically distinct Tregs localized in various nonlymphoid tissue compartments. These tissue Tregs can perform location-specific, alternative functions, highlighting their dynamic, context-dependent roles. Tregs have also been identified in mucosal tissues where specialized physiological functions are paramount, including helping the host to respond appropriately to pathogenic versus innocuous antigens that are abundant at mucosal portals of antigen entry. As in other tissue Treg compartments, mucosal Tregs in the respiratory, gastrointestinal, and genitourinary tracts are distinct from circulating counterparts and can carry out mucosa-specific functions as well as classic suppressive functions that are the hallmark of Tregs. In this review, we summarize current knowledge regarding mucosal Tregs in both health and disease.