Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression

Nikhil N. Kulkarni, Toshiya Takahashi, James A. Sanford, Yun Tong, Adrian F. Gombart, Brian Hinds, Joyce Y. Cheng, Richard L. Gallo

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 an increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. The digestion of double-stranded RNA from keratinocytes exposed to UVB blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells. However, a synthetic noncoding 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 double-stranded RNA and LL-37 was responsible for the endothelial response to keratinocytes. Sequencing of RNA from the endothelial cells uncovered the activation of Gene Ontology (GO) 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 double-stranded RNA and LL-37 promoted adhesion and transmigration of monocytes across the endothelial cell monolayers. Gene knockdown of TLR3, RIGI, or IRF1 decreased monocyte adhesion in endothelial cells, confirming the role of the double-stranded RNA recognition pathways. These observations show how the expression of LL-37 can lead to enhanced sensitivity to UVB radiation in rosacea.

Original languageEnglish
Pages (from-to)645-655.e6
JournalJournal of Investigative Dermatology
Volume140
Issue number3
DOIs
Publication statusPublished - 2020 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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