872 IL-1β is a potential central mediator to Papulopustular Rosacea pathology as determined by paired transcriptomic and proteomic analysis

J. Harden, Y. Shih, D. Rajendran, J. Xu, R. Li, H. Hofland, A.L. Chang

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Papulopustular rosacea (PPR) is a chronic inflammatory skin disease characterized by redness, sensitive skin, and inflammatory lesions. Multiple inflammatory pathways have been described to be upregulated in PPR; however, a complete mechanistic understanding of the central mediators of PPR lesions requires further study. To this end, we quantitatively evaluated both the transcriptomic (RNAseq) and proteomic (OLINK® and MSD®) signature of paired non-lesional (NLS) and lesional (LS) PPR biopsy explants (n=5 patients). We identified 92 differentially expressed genes (DEGs) and 20 differently expressed proteins (DEPs) between paired PPR LS and NLS explants. In confirmation of multiple previous studies, we identified a complex inflammatory milieu in PPR lesional explants, with upregulation of many chemokines, cytokines, and tissue remodeling genes and proteins. MAPK and TNF signaling pathways were the most significantly upregulated pathways in LS tissue, and both signaling pathways highlighted IL-1β as a potential central mediator to PPR pathogenesis. To mechanistically evaluate the role of IL-1β in PPR lesions, we exogenously stimulated NLS explants with IL-1β and performed the same paired transcriptomic and proteomic assessment as described above. IL-1β stimulation of NLS biopsy explants resulted in a transcriptomic and proteomic profile similar to LS PPR. This suggests that even in the absence of de novo influx of immune cells, IL-1β is sufficient to drive a PPR-like profile from NLS tissue-resident cells. Although multiple pathways may play a role in PPR pathology, our paired quantitative transcriptomic and quantitative analysis highlights a potential role of IL-1β in PPR pathogenesis and suggests that targeting this cytokine may be a useful approach for treatment of this disease.
Original languageUndefined/Unknown
Pages (from-to)S114
JournalJournal of Investigative Dermatology
Issue number7, Supplement
Publication statusPublished - 2020

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