Cross Disease Single-Cell Meta-Analysis Deciphers Conserved Pan-Inflammatory Circuits and Divergent Endothelial Rewiring in Inflammatory Skin Pathogenesis.

Skin vascular endothelial cells (VECs) play a crucial role in regulating vascular function, orchestrating local immune responses, and contributing to the progression of immune-mediated inflammatory skin disorders. Despite their importance, the shared and distinct features of VECs across various inflammatory skin conditions remain poorly understood. We analysed single-cell data from 94 skin samples, encompassing healthy individuals and patients with psoriasis, atopic dermatitis, and lupus erythematosus and established a comprehensive VEC atlas spanning multiple inflammatory skin diseases. Our results highlight both common and disease-specific features of VECs, particularly in immune cell activation, angiogenesis, metabolic processes, and intercellular communication. Notably, post-capillary VECs (cluster P) emerged as the most activated subpopulation, exhibiting significant enrichment in pro-inflammatory signalling pathways. Interestingly, cluster P showed distinct pseudotemporal relationships with different VEC clusters across different inflammatory conditions, suggesting disease-specific transcriptional state transitions. Besides, VECs employ both disease-specific ligand-receptor networks to recruit immune cells and remodel stromal niches, alongside conserved mechanisms preserving vascular-immune crosstalk across pathologies. Our study provides a detailed characterisation of VEC pathology in various forms of skin inflammation and offers novel insights into the role of vascular biology in the pathogenesis of skin diseases.