Regulatory T cells in kidney transplantation: mechanisms, therapeutic advances, and future directions

Regulatory T cells (Tregs) play a pivotal role as key modulators of immune tolerance in kidney transplantation, a critical therapeutic approach for end-stage renal disease. Despite advances in surgical techniques and immunosuppressive regimens, kidney transplantation continues to face significant challenges, including immune rejection and complications arising from long-term immunosuppression. In recent years, Tregs have garnered considerable attention due to their potential to promote graft immune tolerance, reduce the reliance on immunosuppressive drugs, and improve transplant outcomes. This review provides a comprehensive overview of the biological characteristics and immunoregulatory mechanisms of Tregs in the context of kidney transplantation. It highlights the clinical relevance of Tregs and summarizes the progress in Treg-based cellular therapies. Special emphasis is placed on emerging molecular pathways regulating Treg function, the role of immune metabolism, and innovative strategies utilizing nanocarrier systems to selectively expand Tregs. Furthermore, the review addresses current challenges in translating Treg research into clinical practice and outlines future research directions aimed at enhancing immune tolerance and graft survival. By synthesizing recent advances, this article aims to offer theoretical support for the clinical application of Treg-mediated immunomodulation in kidney transplantation.