Single-cell sequencing combined with spatial transcriptomics reveals the characteristics of follicle-targeted inflammation patterns in primary cicatricial alopecia

Abstract Background Primary cicatricial alopecia (PCA) causes irreversible hair loss due to immune-mediated hair follicle destruction. This study investigates follicle-targeted inflammation in lichen planopilaris (LPP), a major PCA subtype, to identify therapeutic targets. Methods Scalp samples from...

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Main Authors: Qitao Chen, Yuqian Li, Qilin Zhu, Zhongming Li, Guanghui Shao, Yanjun Liu, Peixuan Jiang, Qiuwei Tao, Lili Shen, Jing Zhu, Linwei Wei, Yanhua Li, Xufeng Du
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cell & Bioscience
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Online Access:https://doi.org/10.1186/s13578-025-01447-1
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Summary:Abstract Background Primary cicatricial alopecia (PCA) causes irreversible hair loss due to immune-mediated hair follicle destruction. This study investigates follicle-targeted inflammation in lichen planopilaris (LPP), a major PCA subtype, to identify therapeutic targets. Methods Scalp samples from LPP, localized scleroderma (LS), and controls were analyzed using single-cell RNA sequencing and spatial transcriptomics. Cellular composition, spatial localization, and intercellular interactions were examined using differential gene expression and ligand-receptor analyses. Results CD8⁺ effector memory T cells (Tem) and macrophages infiltrated hair follicles in LPP, disrupting immune privilege and promoting scarring. Heightened interferon-γ (IFN-γ) signaling and STAT1 activation in Tem cells caused epithelial-mesenchymal transition (EMT) in hair follicle stem cells (HFSCs). Additionally, macrophage-secreted oncostatin M (OSM) impaired HFSC integrity. These mechanisms drive LPP’s inflammation and fibrosis. Conclusions Our findings identify interferon-γ and oncostatin M as key drivers of LPP pathogenesis, offering targets to reduce follicular scarring and preserve hair growth. Trial registration Not applicable. Graphical abstract
ISSN:2045-3701