Comprehensive single-cell transcriptomic reveals different destinies of melanocytes and dynamic changes of immune microenvironment in a psychological stress-induced leukoderma and leukotrichia mouse model

作者：Xuechen Cao, Yongkai Yu, Hang Yao, Yujie Zheng, Jiawei Lu, Yifei Feng, Pei Tu, Ziyu Li, Ming Lu, Yan Lü · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01236-z · 被引用次数：4 · 研究领域：melanin and skin pigmentation、Neuroinflammation and Neurodegeneration Mechanisms、Mast cells and histamine

BACKGROUND: Vitiligo is an acquired skin depigmentation disorder often accompanied by leukoderma and leukotrichia. Half of vitiligo patients experience episodes of stress. METHODS: We established a chronic unpredictable mild stimulation (CUMS) model in C57BL/6 J mice to simulate chronic mental stress-induced leukoderma and leukotrichia. Single-cell RNA sequencing was performed to determine the immune landscape and to characterize the relationship between immune-stromal cells. Immunohistochemistry was employed for validation. RESULTS: We discovered a similar pro-inflammatory micro-environment composed of keratinocytes and fibroblasts similar to that in human vitiligo. Macrophages in CUMS mice expressed high levels of inflammatory factors and were inclined to an M1 pro-inflammatory phenotype. Two distinct clusters of melanocytes were also identified: Mel2, defined as melanocyte stem cells, and Mel3, defined as mature melanocytes. Mel2 cells were prone to pyroptosis and necroptosis, while Mel3 cells were susceptible to oxidative stress, mitochondrial dysfunction, and ferroptosis. Compared with control mice, higher expression of CXCL16 on dendritic cells and of the CXCL16 ligand, CXCR6, on γδT cells were observed in leukoderma. Dendritic cells and natural killer T cells in the CUMS mouse spleen exhibited elevated levels of CXCL16 and CXCR6, respectively. Activation of the CXCL16-CXCR6 axis and a non-specific immune response in our CUMS model might imitate chronic mental stress-in...