Review synthesizes Treg biology and NB-UVB, JAK inhibitors, IL-2 in vitiligo patientsReview shows immune cells may be off in vitiligo

IntroductionVitiligo is an autoimmune skin disorder driven by CD8+ T cell−mediated melanocyte destruction, in which breakdown of immune tolerance plays a pivotal role. Regulatory T cells (Tregs) are central to maintaining peripheral immune tolerance, but their abnormalities in vitiligo remain insufficiently integrated from a systemic perspective.MethodsThis review synthesizes published evidence on Treg biology and immunoregulatory functions, focusing on comparative analyses between peripheral blood and lesional skin of vitiligo patients. We also examine Treg−melanocyte interaction networks, Treg−targeted therapies, and the potential of Treg−related biomarkers.ResultsIn peripheral blood, vitiligo patients exhibit reduced Treg frequency, impaired suppressive capacity, and Th1-like polarization, alongside dysfunctional subsets such as STAM (signal-transducing adaptor molecule)+ Treg and exhausted memory Treg. In lesional skin, tissue−resident and antigen−specific Treg subsets are markedly decreased, and the proinflammatory microenvironment further compromises their function. This systemic−to−local Treg dysregulation leads to insufficient suppression of autoreactive CD8+ T cells and persistent melanocyte destruction. Mechanistically, breakdown of the protective Treg−melanocyte network involves systemic Treg deficits, failure of local tolerance, melanocyte−intrinsic death programs, and disrupted homing/signaling. Therapeutically, NB−UVB, JAK inhibitors, and low−dose IL−2 show promise in restoring immune balance, and emerging Treg subsets may serve as biomarkers for treatment response.DiscussionThe anatomical hierarchy of Treg dysregulation—from blood to skin—underscores that effective immunosuppression requires not only sufficient Treg numbers but also precise tissue localization and functional adaptation. Future single−cell transcriptomics and functionally defined Treg subsets may facilitate translation of Treg−based biomarkers and therapies into practice.