Ultraviolet light exposure suppresses contact hypersensitivity by abrogating endothelial intercellular adhesion molecule-1 up-regulation at the elicitation site.
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.
Komura, K; Hasegawa, M; Hamaguchi, Y; Saito, E; Kaburagi, Y; Yanaba, K; Kawara, S; Takehara, K; Seki, M; Steeber, DA; Tedder, TF; Sato, S
Volume / Issue
Start / End Page
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)