title: Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses.
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.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Milène
authors.initials: M
authors.lastname: Kennedy Crispin
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Johnson-Huang
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Lentini
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; The Center for Clinical and Translational Science, Rockefeller University, New York, New York, USA.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address: kruegej@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D056704:Adaptive Immunity / Q000528:radiation effects; D000328:Adult; D000368:Aged; D001706:Biopsy; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D053492:Elafin / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics* / Q000528:radiation effects; D007113:Immunity, Innate / Q000235:genetics* / Q000528:radiation effects; D007801:Langerhans Cells / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D000067616:S100A12 Protein; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000276:immunology / Q000293:injuries* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; D053492:Elafin; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; C089242:S100A7 protein, human; D023083:beta-Defensins