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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Single-Cell Transcriptomic Analysis Reveals an Inflammatory Antigen-Presenting Macrophages Subtype Drive Vitiligo
Ruozhou Qi1, Min Huang1, Ziyi Lin1
1Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China, bucm.edu.cn.
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.
