Beyond suppression: Treg specialization in infection and tissue repair

Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis and tolerance. While their suppressive function is beneficial in autoimmunity and detrimental in cancer, Tregs also exert essential roles during infections where their functions are nuanced and depend on the context, making their overall role more complex to understand. During infections, Tregs classically dampen excessive immune activation, but this suppression may also allow pathogen persistence. In addition to suppressing excessive inflammation, Tregs can directly promote tissue repair and protection. Recent findings demonstrate that these regenerative properties are also important during infections, where limiting immunopathology and promoting repair are both critical to recovery. Moreover, immune checkpoint molecules such as TIM-3 and TIGIT, classically associated with Treg-mediated suppression, have recently also been suggested to contribute to tissue protection or active repair. Their expression on Tregs raises the possibility that these molecules may support functions beyond immune regulation, potentially participating in the orchestration of tissue repair. This review will focus on how Tregs balance immune suppression and tissue repair during infections, highlighting the importance of these functions for recovery and their potential in developing new therapeutic strategies.