Cross-species comparative spatial transcriptomics of hair follicle-T cell interactions identifies conserved drivers of cutaneous lupus erythematosus skin disease and associated hair loss

This study investigates the interactions between T cells and hair follicles in cutaneous lupus erythematosus (CLE) across mice, dogs, and humans, focusing on the role of these interactions in skin disease and hair loss. The research identifies a 35% overlap in gene expression when autoreactive T cells are transferred in mice, with CD8 T cells contributing to extracellular matrix reorganization. Key findings include the identification of CXCR3 ligands and IFN response genes in hair follicles, conserved across species, and the alleviation of skin disease in mice through CXCR3 knockout on T cells. B cell depletion also reduces skin disease, aligning with human lupus therapies. The study highlights CFD and S100A8/9 as potential targets for future trials, emphasizing the role of CXCR3+ T cells and B cells in CLE lesional skin and their contribution to hair loss and inflammation.