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Meta-Analysis
. 2025 Dec;64(12):2247-2256.
doi: 10.1111/ijd.17959. Epub 2025 Jul 14.

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

Gabriela Lerner  1   2 , Maria Nikolaou  1 , Corinne Stoffel  1 , Eloi Schmauch  3   4   5 , Thomas Kündig  1 , Thierry Passeron  6   7 , Julien Seneschal  8   9 , Nanja van Geel  10 , Ulrike Held  11 , Antonios G A Kolios  1   12
Affiliations
Meta-Analysis

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

Gabriela Lerner et al. Int J Dermatol. 2025 Dec.

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.

Keywords: FOXP3; Treg cells; autoimmunity; dermatology; immune regulation; immunology; regulatory T‐cells; vitiligo.

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Conflict of interest statement

T.P. is a consultant for AbbVie, Almirall, Amgen, Bristol Myers Squibb, Calypso, Galderma, Incyte Corporation, Janssen, Eli Lilly, Novartis, Pfizer, Roivant, UCB, and VYNE Therapeutics. He has received grants and/or honoraria from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol Myers Squibb, Calypso, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Roivant, Sun Pharmaceuticals, UCB, and VYNE Therapeutics. He is the cofounder of YUKIN Therapeutics; and has patents on WNT agonists or GSK3b antagonist for repigmentation of vitiligo and the use of CXCR3B blockers in vitiligo. The other authors declare no conflicts of interest related to this work.

Figures

FIGURE 1
FIGURE 1
The PRISMA flow chart depicts the study selection process. Initially, 1321 studies were identified through searches in Embase, MEDLINE/PubMed, and Scopus, and 308 duplicate articles were excluded. Following screening, 959 articles were removed as irrelevant. A total of 54 reports were requested for retrieval, and their full texts were evaluated for eligibility. Eligible studies were screened through backwards citation searching, resulting in the inclusion of six additional publications. Finally, 21 studies were included in this review, and 18 studies were assessed with meta‐analysis.
FIGURE 2
FIGURE 2
Treg cells quantities in blood. The studies are sorted by the publication year. The diamond represents the summary estimate. The prediction interval gives the range in which a new study's effect estimate will fall.
FIGURE 3
FIGURE 3
Meta‐regression analysis of the association between the proportion of active cases and effect size. Each bubble represents an individual study. The solid line depicts the meta‐regression slope.
FIGURE 4
FIGURE 4
Suppressive capacity of Treg cells on CD4+ and CD8+ T‐cells in blood.
FIGURE 5
FIGURE 5
Levels of IL‐10 in blood.
See this image and copyright information in PMC

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