title: Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of alpha4 integrin.
abstract: OBJECTIVE
  Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine).
  
  
  METHODS
  Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for 'cords formation' were performed as previously described.
  
  
  RESULTS
  Twenty and 40 mJ/cm2 of UVB radiation down-regulated the expression of alpha4 integrin on 24 h-cultured LC, but not that of alpha6, beta1, or beta4 integrin. The number of cultured LC adhered to fibronectin, a ligand for alpha4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for alpha6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the 'cords' formation in dermal vessels of the 48 h-cultured skin.
  
  
  CONCLUSIONS
  These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics.
authors.affiliation: Department of Dermatology, Kansai Medical University, Osaka, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Hamakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Sugihara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horio
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000528:radiation effects*; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000276:immunology*; D020405:Dermis / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology / Q000528:radiation effects*; D007108:Immune Tolerance / Q000276:immunology / Q000528:radiation effects; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014466:Ultraviolet Rays
chemical_list: D039441:Integrin alpha4