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Innate immune dysfunction in rosacea promotes photosensitivity and vascular adhesion molecule expression.

N. Kulkarni,Toshiya Takahashi,J. Sanford,Y. Tong,A. Gombart,B. Hinds,Joyce Y. Cheng,R. Gallo

Published 2020 in Journal of Investigative Dermatology

ABSTRACT

Rosacea is a chronic skin disease characterized by photosensitivity, abnormal dermal vascular behavior, inflammation and enhanced expression of the antimicrobial peptide LL-37. We observed that dermal endothelial cells in rosacea had increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. Digestion of dsRNA from keratinocytes exposed to ultraviolet B radiation (UVB) blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells. However, a synthetic non-coding snoU1RNA was only capable of increasing adhesion molecules on endothelial cells in the presence of LL-37, suggesting that the capacity of UVB exposure to promote both dsRNA and LL-37 was responsible for the endothelial response to keratinocytes. Sequencing of RNA from endothelial cells uncovered activation of gene ontology pathways relevant to the human disease such as type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis and angiogenesis. Functional relevance was demonstrated as dsRNA and LL-37 promoted adhesion and transmigration of monocytes across endothelial cell monolayers. Gene knock down of TLR3, RIGI or IRF1 decreased monocyte adhesion endothelial cells, confirming the role of dsRNA recognition pathways. These observations show how expression of LL-37 can lead to enhanced sensitivity to UVB radiation in rosacea.

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