Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses

Milène Kennedy Crispin, Judilyn Fuentes-Duculan, Nicholas Gulati, Leanne M. Johnson-Huang, Tim Lentini, Mary Sullivan-Whalen, Patricia Gilleaudeau, Inna Cueto, Mayte Suárez-Fariñas, Michelle A. Lowes, James G. Krueger

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The acute response of human skin to UVB radiation has not been fully characterized. We sought to define the cutaneous response at 24 hours following narrowband UVB (NB-UVB, 312-nm peak), a therapeutically relevant source of UVB, using transcriptional profiling, immunohistochemistry, and immunofluorescence. There were 1,522 unique differentially regulated genes, including upregulated genes encoding antimicrobial peptides (AMPs) (S100A7, S100A12, human beta-defensin 2, and elafin), as well as neutrophil and monocyte/dendritic cell (DC) chemoattractants (IL-8, CXCL1, CCL20, CCL2). Ingenuity pathway analysis demonstrated activation of innate defense and early adaptive immune pathways. Immunohistochemistry confirmed increased epidermal staining for AMPs (S100A7, S100A12, human beta-defensin 2, and elafin). Inflammatory myeloid CD11c + BDCA1-DCs were increased in irradiated skin, which were immature as shown by minimal colocalization with DC-LAMP, and coexpressed inflammatory markers tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand in irradiated skin. There were increased BDCA3 + DCs, a cross-presenting DC subtype with immunosuppressive functions, and these cells have not been previously characterized as part of the response to UVB. These results show that the acute response of human skin to erythemogenic doses of NB-UVB includes activation of innate defense mechanisms, as well as early infiltration of multiple subtypes of inflammatory DCs, which could serve as a link between innate and adaptive immunity.

Original languageEnglish (US)
Pages (from-to)692-701
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number3
DOIs
StatePublished - Mar 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Kennedy Crispin, M., Fuentes-Duculan, J., Gulati, N., Johnson-Huang, L. M., Lentini, T., Sullivan-Whalen, M., Gilleaudeau, P., Cueto, I., Suárez-Fariñas, M., Lowes, M. A., & Krueger, J. G. (2013). Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses. Journal of Investigative Dermatology, 133(3), 692-701. https://doi.org/10.1038/jid.2012.359