title: Whole body irradiation induces cutaneous dendritic cells depletion via NF-κB activation.
abstract: BACKGROUND
  Effect of ionizing radiation on cutaneous dendritic cells (cDC) is critical to its influence on immune status of the skin, which plays an important role in the progression and recovery of radiation skin sickness. This study was to study the influence of whole body irradiation (WBI) on the cDC.
  
  
  METHODS
  Density of epidermal and dermal DC was determined with a fluorescent microscopy and the DC numbers in lymph node were measured by flow cytometry. A FITC induced migration assay was also used to study the migration of DC. The expressions of cytokines and chemokines were evaluated by Realtime PCR, and the protein level of was measured by Western blot.
  
  
  RESULTS
  WBI caused depletion of cDC in epidermal as well as dermal and augmented FITC-induced migration of DC to the draining lymph node (LN). The number of DC migrated from ear explants to the CCL19-containing medium also increased after exposure to WBI. It was also found that WBI increased mRNA level of CCL19/CCL21 as well as CCR7 in LN and skin tissue. The expressions of TNFα, IL-1α, IL-1β, and IL-6 in skin tissues were also greatly induced by WBI in a dose dependent manner. Finally, we found that WBI induced translocation of nuclear factor κB (NF-κB) and that the radiation-induced migration of DC was blocked by NF-κB inhibitor or TLR4 knockout.
  
  
  CONCLUSIONS
  WBI caused cDC depletion through induction of DC migration to the draining LN, which might result from the activation of NF-κB and the induction of inflammatory microenvironment within the skin.
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, P.R. China.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Yang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cui
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000528:radiation effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D008198:Lymph Nodes / Q000166:cytology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013859:Thiocarbamates / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014916:Whole-Body Irradiation
chemical_list: D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D013859:Thiocarbamates; D051197:Toll-Like Receptor 4; C066229:prolinedithiocarbamate; D011392:Proline