Work

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

Year: 2025

Type: article

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.

Source: Cell & Bioscience

DOI: 10.1186/s13578-025-01447-1