Comparative Spatial Transcriptomics of Hair Follicle-T Cell Interactions in Mouse, Dog, and Human Reveals Conserved Drivers of Primary Cicatricial Alopecia

January 2025 in “ bioRxiv (Cold Spring Harbor Laboratory) ”

Ümmügülsüm Yıldız-Altay, Rutha Adhanom, Warda Abdi, Andrew Romasco, Linlin You, Elise Santacruz, Saeed Shakiba, Mridushi Daga, Qi Tang, Marı́a I. Olivera, Thomas Cicuto, Floriane Bretheau, Christina E. Baer, Motahareh Arjomandnejad, Allison M. Keeler, Helen Bui, Babak Shokrani, Ramón Almela, Angel S. Byrd, Christian Frey, Jillian M. Richmond

primary cicatricial alopecia autoimmune disorders scarring hair loss T cell-hair follicle interactions spatial transcriptomics CXCR3 ligands IFN response genes CD34+ bulge cells keratinocytes fibrosis CFD S100A8/9 immune system hair follicle inflammation

TLDR Potential therapeutic targets for scarring hair loss are identified.

The study investigates primary cicatricial alopecias (PCA), a group of autoimmune disorders causing scarring hair loss, by examining T cell-hair follicle interactions across mice, dogs, and humans. Using spatial transcriptomics, the research identifies conserved pathways involving T cells and hair follicles, such as CXCR3 ligands and IFN response genes, which are consistent across species. The study highlights the loss of CD34+ bulge cells and keratinocytes in a mouse model, with fibrosis development confirmed through histology. Novel drug-targetable pathways, CFD and S100A8/9, are proposed for further exploration in treating these conditions. The findings suggest potential therapeutic targets for PCA, with implications for both veterinary and human medicine.

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