Single-Cell RNA-seq Reveals Increased and Activated Post-Capillary Venule Endothelial Cells in Erythrodermic Psoriasis.

Erythrodermic psoriasis (EP) is a life-threatening variant of psoriasis. In this study, we contrasted the vascular endothelial cells (ECs) in EP lesions against those in psoriasis vulgaris and healthy controls. Utilizing single-cell RNA sequencing, immunofluorescence, and flow cytometry on human and mouse samples, we observed a marked increase and activation of EP ECs, which upregulated genes relative to angiogenesis, leukocyte adhesion and antigen presentation. This was particularly evident in the subpopulation post-capillary venules (PCV), especially the cluster from EP. Cell-cell communication studies revealed intensified interactions between PCV and leukocytes, mediated by SELE and ICAM1, predominantly in EP. Trajectory analysis suggested differentiation direction of venules-PCV-CAP. 1 with a concomitant reduction in NF2R2 expression. Elevated and activated PCVs were found in EP patient biopsies and mouse models. These findings underscore the significance of PCV in EP pathogenesis, presenting new therapeutic avenues for this debilitating disease.