Meta-analysis of RNA sequencing data from 534 skin samples shows substantial IL-17 effects in non-lesional psoriatic skin

Abstract

ABSTRACTPsoriasis is a common chronic inflammatory skin disease characterized by disturbed interactions between infiltrating immune cells and keratinocytes. To enhance our understanding of the underlying molecular and cellular mechanisms driving psoriasis pathobiology, and to identify potential biomarkers for disease severity, we conducted RNA sequencing of skin biopsies from 75 patients with psoriasis vulgaris and 46 non-psoriatic controls. To increase the robustness of the results, we meta-analysed our data with four publicly available datasets, bringing the total number of samples to 534. By comparing lesional psoriatic (PP) to healthy control (NN) skin, we identified 2269 differentially expressed genes (DEGs) (|log2FC|>1.0, FDR <0.1), and 58 DEGs when comparing non-lesional psoriatic (PN) to NN skin. We also identified 54 DEGs associated with disease severity (PASI ≥10 vs. PASI <10). Cellular deconvolution analysis showed that differentiated keratinocytes emerged as the most prominent cell type among the DEGs in PP/NN. Functional enrichment analysis in PN/NN revealed several IL-17 related pathways and confirmed a previously reported ‘pre-inflammatory signature’ across all psoriatic skin. This study provides insights into the psoriasis transcriptome and identifies a severity-specific signature, which may serve as candidate for future studies aimed at identifying psoriasis biomarkers and predicting disease progression.