Mediators of Inflammation - Research Article - Single-Cell Transcriptomic Analysis Reveals an Inflammatory Antigen-Presenting Macrophages Subtype Drive Vitiligo Pathogenesis Through STAT1-Mediated Dual Mechanisms

Sep 29, 2026

Single-cell transcriptomic analysis combined with experimental validation dissects macrophage heterogeneity in vitiligo, a progressive depigmentary disorder marked by melanocyte loss. scRNA-seq from healthy and vitiligo-affected skin reveals enriched T-cell subsets and five macrophage subpopulations, including inflammatory antigen-presenting macrophages (Mac-InﬂamAP). Mac-InﬂamAP acts as a terminal differentiation state, inhibits melanocytes via TNF-mediated effects while enhancing antigen presentation to promote melanocyte loss. STAT1 is identified as a key regulator, and its suppression ameliorates disease by reducing T-cell activation and macrophage M1 polarization.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Vitiligo background and immune mechanisms

Role of macrophage heterogeneity

Methods and Results

Single-cell RNA sequencing and computational analyses

STAT1 suppression and experimental validation

Conclusions

Wiley Mediators of Inflammation Volume 2025, Article ID 8878698, 18 pages [https://doi.org/10.1155/mi/8878698](https://doi.org/10.1155/mi/8878698) Research Article Single-Cell Transcriptomic Analysis Reveals an Inﬂammatory Antigen-Presenting Macrophages Subtype Drive Vitiligo Pathogenesis Through STAT1-Mediated Dual Mechanisms Ruozhou Qi , Min Huang , Ziyi Lin , Huanhuan Deng , Rule Sa , Yi Chen , Guangshan Chen , and Xingwu Duan Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China Correspondence should be addressed to Guangshan Chen; cgs880802@sina.com and Xingwu Duan; [a02205@bucm.edu.cn](a02205@bucm.edu.cn) Received 23 September 2025; Revised 20 October 2025; Accepted 27 November 2025 Guest Editor: Liu Jinhui Copyright © 2025 Ruozhou Qi et al. Mediators ofInﬂammation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Background: Vitiligo is a common depigmentary disorder characterized by progressive melanocyte (MEL) loss. While T-cell activation is central to its pathogenesis, the role of macrophages remains poorly understood. This study characterizes macrophage heterogeneity and function in vitiligo using single-cell transcriptomic analysis and experimental validation. Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from healthy and vitiligo-affected skin to identify macrophage subpopulations. Computational analyses included cell subpopulation clustering, pseudotime trajectory inference, cell–cell communication, and high-dimensional weighted gene coexpression network analysis (hdWGCNA) . In vivo and in vitro experiments examined the effects of STAT1 suppression on the macrophage inﬂammatory phenotype and antigen presentation capacity. Results: scRNA-seq analysis identiﬁed macrophages and T cell subsets enriched in vitiligo. Macrophage subclustering identiﬁed ﬁve subpopulations, with inﬂammatory antigen-presenting macrophages (Mac-InﬂamAP) signiﬁcantly enriched in vitiligo lesions and M1-polarized. Pseudotime analysis revealed Mac-InﬂamAP as a terminal differentiation state. Cell–cell communication analysis showed Mac-InﬂamAP exerts TNF-mediated inhibitory effects on MELs while enhancing T-cell antigen presentation, thereby promoting MEL loss. hdWGCNA identiﬁed STAT1 as a key regulator highly expressed in Mac-InﬂamAP. In vivo, STAT1 inhibition by ﬂudarabine ameliorated vitiligo progression by suppressing T cell activation and macrophage M1-polarization. In vitro experiments conﬁrmed STAT1 suppression reduced macrophage M1 polarization, inﬂammatory phenotype, and antigen presentation capabilities. Conclusions: This study reveals an uncharacterized inﬂammatory macrophage subpopulation crucial to vitiligo pathogenesis through dual mechanisms: direct MEL inhibition and enhanced T-cell activation. The identiﬁcation of STAT1 as a key regulatory molecule provides a novel therapeutic target for vitiligo. These ﬁndings advance our understanding of immune-mediated mechanisms in vitiligo. Keywords: macrophages; melanocytes; single-cell RNA sequencing; STAT1; vitiligo 1. Introduction Vitiligo is a common acquired depigmentary disorder affecting approximately 0.5%–2% of the global population, with profound psychological and social impacts worldwide [1] . The disease is characterized by the progressive loss of melanocytes (MELs), resulting in well-deﬁned depigmented patches on the skin and mucous membranes [2, 3] . Current knowledge of vitiligo pathogenesis highlights a multifactorial process involving genetic predisposition, environmental triggers, and immune dysregulation, which together drive MEL destruction through both innate and adaptive immune mechanisms [4–6] . Extensive evidence has established that autoreactive cytotoxic T cells are central med

FAQs

What is the main aim of this study on vitiligo?

To characterize macrophage heterogeneity and function in vitiligo using single-cell transcriptomic analysis and experimental validation, focusing on how specific macrophage subtypes drive pathogenesis.

Which macrophage subtype is highlighted as crucial?

Inflammatory antigen-presenting macrophages (Mac-InﬂamAP), found to be significantly enriched in vitiligo lesions and to display M1 polarization with a terminal differentiation state.

How does STAT1 relate to vitiligo progression here?

STAT1 is identified as a key regulator highly expressed in Mac-InﬂamAP. Inhibition of STAT1 suppresses T-cell activation and macrophage M1 polarization, ameliorating vitiligo progression.

Sep 29, 2026

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