Pathogenic hallmarks of primary lymphocyte-mediated scarring alopecia revealed by single nuclear and spatial multiomics

Summary: Abstract Body: Primary lymphocyte-mediated scarring alopecias (PLSA) are characterized by autoimmune attack and loss of hair follicle stem cells and perifollicular scarring. To better understand the pathogenesis of PLSA, paired single nuclear RNA sequencing (snFFPEseq) and Visium spatial transcriptomics were performed on archived patient samples from two healthy scalp skin specimens and six PLSA specimens. snFFPEseq demonstrated increased percentages CD4+ T effector cells, CD8+ T cells, and B cells in PLSA biopsies. Furthermore, analysis of keratinocyte and fibroblast clusters demonstrated increased numbers of cells with an epithelial-to-mesenchymal (EMT) signature in the scarring alopecia specimens. Visium spatial transcriptomics confirmed that the EMT signature was restricted to the interface of damaged hair follicle keratinocytes and perifollicular concentric fibrosis. Additionally, Xenium spatial transcriptomics performed on non-paired patient samples showed expression of EMT genes, such as POSTN, GREM1, and INHBA in KRT15+ hair follicle keratinocytes undergoing autoimmune attack and in adjacent sclerosing fibroblasts. CD8+ T cells expressing IFNG and GZMB were also major immune constituents at pathogenic interface zones. Overall, there is emerging evidence that effector T cells and B cells are associated with and EMT gene signature in pathogenic regions of PLSA. Gayatri Kolluri¹, Sean Clancy¹, Jarish Cohen¹ 1. Dermatology, University of California San Francisco, San Francisco, CA, United States. Translational Studies: Cell and Molecular Biology