Cross-species insights into hair follicle-T cell interactions in discoid lupus erythematosus: A comparison of human, canine and mouse models using spatial transcriptomics

Summary: Abstract Body: Discoid lupus erythematosus (DLE) is a type of primary cicatricial alopecia (PCA), causes scarring hair loss via lymphocytic inflammation. To explore the mechanism of disease, we performed spatial transcriptomics across humans,dogs with spontaneous DLE and a novel murine PCA model. This cross-species study sought to identify shared molecular pathways and potential therapeutic targets. In human DLE, perifollicular T cells were significantly enriched and showed increase gene expression of CXCR3 ligands (e.g., CXCL9, CXCL11) , interferon-response genes (e.g. IRF7, ISG15), and fibrotic markers. These findings suggest robust immune activation and extracellular matrix remodeling in the hair follicle, contributing to follicular damage and scarring. Similarly, canine DLE samples demonstrated immune cell infiltration around hair follicles with elevated gene levels of S100A8/9 and loss of protective elements such as PPARG, supporting the relevance of canine DLE as a translational model for human disease. In PCA mouse model, CD8+ T cells were observed to arrest near hair follicles, leading to the depletion of CD34+ bulge stem cells and subsequent fibrosis. Comparing gene expression in the hair follicle from PCA vs healthy mice revealed many differentially expressed genes, including ATF4, an upregulated transcription factor involved in the integrated stress response .Comparative transcriptomic analysis across species highlighted overlapping pathways, including interferon signaling and complement activation. Notably, therapeutic targets such as CFD and S100A8/9 were identified across human, canine and murine samples. These genes, implicated in keratinocyte activation and immune regulation, represent promising candidates for developing new treatments. Conservation of these pathways highlights the potential for cross-species therapeutic trials to benefit both veterinary and human medicine. Ummugulsum Yildiz Altay^{2, 1}, Rutha Adhanom¹, Lauren You¹, Saeed Shakiba¹, Jillian Richmond¹ 1. Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, United States. 2. Dermatology, Yale University School of Medicine, New Haven, CT, United States. Adaptive and Auto-Immunity