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-α production after Ag challenge at elicitation sites. Local TNF-α injection before elicitation abrogated the UV-induced CHS inhibition with increased endothelial ICAM-1 expression. TNF-α 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.

CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue

“…Another possible mechanism is IL-10-induced downregulation of TNF-a at the site of inflammation, which subsequently results in abrogation of the up-regulation of endothelial ICAM-1 and inhibition of CHS, as shown for IL-10 produced by UV-induced suppressor T cells [23]. A similar mechanism was described by Sasaki et al, who demonstrated that in IL-10-transfected endothelial cultures, the expression of TNF-a-induced MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is significantly reduced and, consequently, the MAdCAM-1-dependent lymphocyte adhesion inhibited [24].…”

Current concepts of the cellular and molecular pathophysiology of multiple sclerosis

“…ICAM-1 is widely expressed on T and B cells as well as monocytes and endothelium (Dustin and Springer, 1991). It plays a role in enhancing effector T cell responses (Berton and Lowell, 1999;Komura et al, 2003) and in the adherence of mononuclear cells to endothelium (Springer, 1994), including the blood-brain barrier (Greenwood et al, 2002). Altered levels of expression or function of ICAM-1 could occur via both of these mechanisms and influence the pathogenesis of MS. TCR signaling is mediated and regulated by a number of molecules.…”

Low Zone Tolerance Requires ICAM-1 Expression to Limit Contact Hypersensitivity Elicitation

“…Previous studies have revealed that ICAM-1 is highly expressed on endothelium within the skin (Komura et al, 2003;McHale et al, 1999). Therefore, the major source of ICAM-1 mRNA in the current study is likely to be endothelial cells.…”

“…Previous studies have shown that UV-induced suppressor cells can attenuate the elicitation phase of CHS as well as the sensitization phase (Komura et al, 2003). To assess the function of low dose tolerization-induced suppressor cells on the elicitation phase, we conducted further adoptive transfer studies.…”