Single-cell and spatial transcriptomics implicate vascular cell orchestration of inflammatory changes after UV light...

To elucidate the complex effects of acute UVR on the skin, we exposed mouse skin to UVB and performed transcriptomic profiling of the epidermis, deep dermis, and adipose tissue. Spatial transcriptomic analysis revealed gene expression changes in the epidermis, dermis, and adipose. Whereas CD45⁺ immune cells showed differential expression of chemokines, cytokines, and acute-phase proteins, cytokeratin⁺ epidermal cells upregulated genes related to cellular stress and damage, structural remodeling, and apoptosis. Single-cell RNA sequencing 12 hours after UVR identified 4849 differentially expressed genes, with the epidermis and endothelial cells showing the highest differentially expressed gene counts. Pathway analysis of upregulated genes in the epidermis revealed enrichment in VEGF, HIPPO, complement, IL-6, and apoptosis signaling pathways. In endothelial cells, receptor-ligand analysis highlighted endothelial cells as key targets of CXCL chemokines and C3. In fibroblasts, UVR triggered the upregulation of inflammatory activation markers alongside genes associated with glucose metabolism. Cross-species comparison of UVR-responsive differentially expressed genes between mice and humans revealed strong concordance, particularly in TGF-β- and TNF-associated pathways. These results highlight the sequential activation of keratinocytes, fibroblasts, endothelial, and immune cells, providing mechanistic insights into how UVR can initiate or exacerbate autoimmune processes such as those observed in cutaneous lupus.