Document Detail


Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses.
MedLine Citation:
PMID:  23151847     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-15
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  133     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-12     Completed Date:  2013-06-20     Revised Date:  2014-11-16    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  692-701     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptive Immunity / radiation effects
Adult
Aged
Biopsy
Cell Movement / radiation effects
Cell Proliferation / radiation effects
Elafin / genetics,  metabolism
Female
Gene Expression Profiling*
Humans
Immunity, Cellular / genetics*,  radiation effects
Immunity, Innate / genetics*,  radiation effects
Langerhans Cells / pathology,  radiation effects
Male
Middle Aged
S100 Proteins / genetics,  metabolism
Signal Transduction / radiation effects
Skin / immunology,  injuries*,  radiation effects*
Ultraviolet Rays / adverse effects*
beta-Defensins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
1R01AR060222/AR/NIAMS NIH HHS; 3K23AR052404-04S1/AR/NIAMS NIH HHS; GM07739/GM/NIGMS NIH HHS; R01 AR060222/AR/NIAMS NIH HHS; T32 GM007739/GM/NIGMS NIH HHS; UL1 RR024143/RR/NCRR NIH HHS; UL1 RR024143/RR/NCRR NIH HHS; UL1 TR000043/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/DEFB4A protein, human; 0/Elafin; 0/S100 Proteins; 0/S100A12 protein, human; 0/S100A7 protein, human; 0/beta-Defensins
Comments/Corrections

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