Mediators of capillary-to-venule conversion in the chronic inflammatory skin disease psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and hyperkeratosis, immune cell infiltration and vascular remodeling. Despite the emerging recognition of vascular normalization as a potential strategy in managing psoriasis, an in-depth delineation of the remodeled dermal vasculature has been missing. In the present study, we exploited 5' single-cell RNA-sequencing (scRNA-seq) to investigate the transcriptomic alterations in different subpopulations of blood vascular and lymphatic endothelial cells (ECs) directly isolated from psoriatic and healthy human skin. Individual subtypes of ECs underwent specific molecular repatterning associated with cell adhesion and extracellular matrix organization. Blood capillaries, in particular, showed upregulation of the melanoma cell adhesion molecule (MCAM) as well as its binding partners and adopted post-capillary venule-like characteristics during chronic inflammation that are more permissive to leukocyte transmigration. We also identified psoriasis-specific interactions between cis-regulatory enhancers and promoters for each EC subtype, revealing the dysregulated gene regulatory networks in psoriasis. Together, our results provide more insights into the specific transcriptional responses and epigenetic signatures of ECs lining different vessel compartments in chronic skin inflammation.