Beyond immune suppression: regenerative programs in regulatory T cells.

Regulatory T cells (Tregs) are traditionally recognized for their indispensable roles in maintaining immune tolerance and suppressing excessive inflammation. However, accumulating evidence has revealed an unexpected regenerative dimension of Treg biology across multiple tissues. Here, regenerative function refers to the capacity of Tregs to directly regulate stem cells, stromal cells, epithelial cells, and other non-immune tissue cells through specialized reparative mediators, thereby contributing to restoration of tissue structure, cellular composition, or function. Emerging studies demonstrate that these regenerative activities are triggered by tissue injury and coordinated by diverse reparative signals. Notably, in selected experimental settings, specific tissue-regenerative pathways can be mechanistically distinguished from canonical immune-regulatory functions of Tregs, although these programs frequently operate in a coordinated and complementary manner during physiological tissue restoration. In this review, we summarize tissue-adapted regenerative programs employed by Tregs across diverse organs, discuss common principles underlying regenerative Treg biology, and evaluate evidence for dedicated regenerative Treg states. Finally, we propose a conceptual framework in which Tregs function as dual-purpose regulators of both immune homeostasis and tissue restoration, highlighting their broader significance in physiology, disease, and regenerative medicine.