炎症性皮膚疾患における疾患横断的単一細胞メタ解析による炎症回路と内皮再配線の解読

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.