Pathogenic Hallmarks of Primary Lymphocyte-Mediated Scarring Alopecia Revealed by Single Nuclear and Spatial Multiomics

July 2025 in “ Journal of Investigative Dermatology ”

Gautham Kolluri, Steven J. Clancy, Justine V. Cohen

scarring alopecia primary lymphocyte-mediated scarring alopecia PLSA CD4+ T effector cells CD8+ T cells B cells keratinocyte fibroblast epithelial-to-mesenchymal transition EMT hair follicle perifollicular fibrosis POSTN GREM1 INHBA KRT15+ keratinocytes IFNG GZMB

TLDR Scarring alopecia involves increased immune cells and specific gene changes near damaged hair follicles.

The study investigates the pathogenesis of primary lymphocyte-mediated scarring alopecias (PLSA) using single nuclear RNA sequencing and spatial transcriptomics on samples from two healthy and six PLSA-affected scalps. Findings reveal increased CD4+ T effector cells, CD8+ T cells, and B cells in PLSA, alongside keratinocyte and fibroblast clusters with an epithelial-to-mesenchymal transition (EMT) signature. This EMT signature is localized at the interface of damaged hair follicle keratinocytes and perifollicular fibrosis. Key EMT genes, such as POSTN, GREM1, and INHBA, are expressed in KRT15+ keratinocytes and adjacent fibroblasts under autoimmune attack. CD8+ T cells expressing IFNG and GZMB are prominent at these pathogenic zones, suggesting a link between effector T cells, B cells, and EMT gene expression in PLSA.

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