TY - JOUR
T1 - Gene profiling of narrowband UVB-induced skin injury defines cellular and molecular innate immune responses
AU - Kennedy Crispin, Milène
AU - Fuentes-Duculan, Judilyn
AU - Gulati, Nicholas
AU - Johnson-Huang, Leanne M.
AU - Lentini, Tim
AU - Sullivan-Whalen, Mary
AU - Gilleaudeau, Patricia
AU - Cueto, Inna
AU - Suárez-Fariñas, Mayte
AU - Lowes, Michelle A.
AU - Krueger, James G.
N1 - Funding Information:
This research was supported by National Institutes of Health (NIH) grant UL1 RR024143 from the National Center for Research Resources and the Milstein Medical Program. NG was supported by NIH MSTP grant GM07739. TL is supported by 3K23AR052404-04S1; MAL is supported by NIH 1R01AR060222; LMJ-H is supported by the Linda and Leonard Berkowitz Postdoctoral Fellowship.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2012.359
DO - 10.1038/jid.2012.359
M3 - Article
C2 - 23151847
AN - SCOPUS:84873732212
SN - 0022-202X
VL - 133
SP - 692
EP - 701
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -