Multitranscriptome Analysis Revealed That Stromal Cells in the Papillary Dermis Promote Angiogenesis in Psoriasis Vulgaris.

BACKGROUND:The pathogenesis of psoriasis, an inflammatory skin disease, is incompletely understood. Growing evidence substantiates the involvement of stromal cells in the inflammatory process. OBJECTIVES:To investigate the roles of stromal cells, including fibroblasts, vascular endothelial cells (VECs) and smooth muscle cells (VSMCs), in the psoriatic inflammatory microenvironment and the possible underlying mechanisms involved. METHODS:This study employed combination of single-cell, spatial transcriptome and bulk RNA sequencing using lesional and nonlesional skin samples from patients with psoriasis vulgaris (PV) and healthy skin samples from unaffected individuals. RESULTS:Through the analysis of transcriptome from 364,098 single cells, we uncovered WNT5A+ fibroblasts, ITIH5+ VECs and VCAN+ VSMCs with the significantly increased cell proportions in the papillary dermis of lesional skin. We defined eight unique subclusters of fibroblasts in the skin and observed a shift of WIF1+ fibroblasts towards WNT5A+ fibroblasts, with abnormal activation of the non-canonical Wnt signaling pathway and increased capabilities of angiogenesis and pro-inflammatory. For the microvascular cells, VSMCs could undergo phenotypic transformation from a contractile phenotype to a synthetic phenotype in the development of psoriatic inflammation. ITIH5+ VECs and VCAN+ VSMCs were identified with an essential role in regulating angiogenesis and vascular remodeling involved in the mechanism of psoriatic pathological changes. Ligand receptor analyses demonstrated WNT5A+ fibroblasts were extensively implicated in interactions with various cell types in skin, especially with ITIH5+ VECs and VCAN+ VSMCs within the papillary dermis. CONCLUSIONS:Interactions of stromal cells in the papillary dermis were identified as possible pathogenic elements in psoriasis vulgaris. Improving the inflammatory microenvironment by targeting stromal cells might be a potential treatment strategy for psoriasis.