Regulatory T Cell Dysregulation in Vitiligo: A Meta-Analysis and Systematic Review of Immune Mechanisms and Therapeutic Perspectives.

Abstract

Vitiligo is an autoimmune disorder marked by the progressive loss of skin melanocytes, increasingly linked to immune dysregulation as a key driver of disease onset and progression. Regulatory T (Treg) cells are essential for maintaining immune homeostasis by suppressing autoreactive immune responses. Mounting evidence implicates functional and numerical alterations in Treg cells in the pathogenesis of vitiligo. This study reviews findings on lesional and circulating Treg cells in vitiligo patients compared to healthy controls (HCs), examining Treg cell frequency, their ability to suppress CD4⁺ and CD8⁺ T cell activity, levels of the immunoregulatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), expression of the key suppressive marker FOXP3, as well as levels of the pro-inflammatory cytokines interleukin-17 (IL-17) and interleukin-22 (IL-22). A comprehensive systematic search was performed across Embase, MEDLINE/PubMed, and Scopus databases to identify eligible studies. A total of 21 studies comprising 1016 vitiligo patients and 846 HCs were included in the review. The analysis revealed a significant reduction in peripheral Treg cell counts (p = 0.01), impaired overall suppressive capacity of CD4+ and CD8+ T cells (p = 0.01), reduced levels of IL-10 (p = 0.02), increased levels of IL-17 (p ≤ 0.01) and IL-22 (p ≤ 0.01) in the blood of vitiligo patients compared to HCs. No statistically significant difference was observed in circulating TGF-β levels (p = 0.1). Most studies reported reduced FOXP3 expression in both skin and blood of vitiligo patients. Current evidence suggests vitiligo involves both reduced numbers and impaired function of Treg cells, supporting further study of Treg pathways as targets for immunomodulatory therapy.