Paired Transcriptomic and Proteomic Analysis Implicates IL-1β in the Pathogenesis of Papulopustular Rosacea Explants

Papulopustular rosacea (PPR) is a chronic inflammatory skin disease with limited treatment options. Although multiple pathways have been described to be upregulated in PPR, a mechanistic understanding of the key drivers and interaction between pathways in PPR pathology is lacking. In this study, we utilized PPR biopsy explants to integrate both differentially expressed genes (DEGs) and differently expressed proteins (DEPs) in paired non-lesional (NL) and lesional (LS) PPR tissue (n=5 patients). The results of this study identified 92 DEGs and 20 DEPs between paired PPR LS and NL explants. MAPK and TNF signaling pathways were the most significantly upregulated pathways in PPR LS tissue and aligned with DEPs identified in this study. Both MAPK and TNF signaling pathways highlighted IL-1β as a potential central mediator to PPR pathogenesis. In support of this, stimulation of NL explants with IL-1β resulted in a transcriptomic and proteomic profile similar to LS PPR. In this integrative transcriptomic and quantitative protein analysis, we identified several inflammatory genes, proteins, and pathways which may be contributing to PPR, as well as highlighted a potential role of IL-1β in driving inflammation in PPR.