title: Ultraviolet light exposure suppresses contact hypersensitivity by abrogating endothelial intercellular adhesion molecule-1 up-regulation at the elicitation site.
abstract: Hapten sensitization through UV-exposed skin induces systemic immune suppression, which is experimentally demonstrated by inhibition of contact hypersensitivity (CHS). Although this UV-induced effect has been shown to be mediated by inhibition of the afferent phase of the CHS, the UV effects on the efferent (elicitation) phase remain unknown. In this study, UV effects on endothelial ICAM-1 expression at elicitation sites were first examined. Mice were sensitized by hapten application onto UV-exposed back skin, and ears were challenged 5 days later. ICAM-1 up-regulation at nonirradiated elicitation sites following hapten challenge was eliminated by UV exposure on sensitization sites distant from elicitation sites. To assess whether loss of the ICAM-1 up-regulation at elicitation sites contributed to UV-induced immunosuppression, we examined CHS responses in UV-exposed ICAM-1-deficient (ICAM-1(-/-)) mice that genetically lacked the ICAM-1 up-regulation. ICAM-1(-/-) mice exhibited reduced CHS responses without UV exposure, but UV exposure did not further reduce CHS responses in ICAM-1(-/-) mice. Furthermore, ICAM-1 deficiency did not affect the afferent limb, because ICAM-1(-/-) mice had normal generation of hapten-specific suppressor and effector T cells. This UV-induced immunosuppression was associated with a lack of TNF-alpha production after Ag challenge at elicitation sites. Local TNF-alpha injection before elicitation abrogated the UV-induced CHS inhibition with increased endothelial ICAM-1 expression. TNF-alpha production at elicitation sites was down-regulated by IL-10, a possible mediator produced by hapten-specific suppressor T cells that are generated by UV exposure. These results indicate that UV exposure inhibits CHS by abrogating up-regulation of endothelial ICAM-1 expression after Ag challenge at elicitation sites.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.forename: Eriko
authors.initials: E
authors.lastname: Saito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kaburagi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yanaba
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Makoto
authors.initials: M
authors.lastname: Seki
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D007165:Immunosuppression Therapy; D007271:Injections, Intradermal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D016753:Interleukin-10 / Q000276:immunology; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology / Q000528:radiation effects*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10