Meta-analysis of single-cell RNA sequencing data of human psoriasis implicates IL-32-expressing fibroblasts in disease pathogenesis

Summary: Abstract Body: Psoriasis is a chronic inflammatory autoimmune skin condition primarily mediated by immune cells and keratinocytes, however, the contribution of fibroblasts to psoriasis pathogenesis remains underexplored. Emerging evidence suggests that fibroblasts express pro-inflammatory mediators IL36 and CXCL2/12, which recruit Tc17 cells and neutrophils. To investigate the role of fibroblasts in psoriasis, we performed a meta-analysis of four single-cell RNA sequencing (scRNA-sequencing) datasets from keyword-based search of literature on the Gene Expression Omnibus database. The aggregate scRNA-sequecing data comprised 15 control skin samples, 26 untreated psoriatic lesions, and 3 treated psoriatic lesions from 35 unique patients. Integrated analysis of 121,000 cells revealed diverse cell types, including fibroblasts, keratinocytes, endothelial cells, and immune cells. Among fibroblast subpopulations, one expressing IL32 was significantly enriched in psoriatic lesions compared to controls (33% vs. <1%, p<0.01). Treated psoriatic lesions exhibited a relative reduction in this subpopulation (24% treated vs. 33% untreated, p=0.62). As a proinflammatory cytokine, IL32 amplifies local inflammation through initiating downstream cytokine release. These findings reveal an active role of IL32-expressing fibroblasts in psoriasis pathogenesis, extending their function beyond canonical stromal support. Targeting fibroblast-mediated pathways represents a promising therapeutic strategy for addressing psoriatic inflammation. Hanqi Yao¹, John Lu¹, Michael Januszyk¹, Dayan Li¹, Michael Longaker¹, Derrick Wan¹ 1. Stanford University School of Medicine, Stanford, CA, United States. Bioinformatics, Computational Biology, and Imaging