IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis

Antonopoulos, C., Cumberbatch, M., Mee, J. B., Dearman, R. J., Wei, X.-Q., Liew, F. Y., Kimber, I. and Groves, R. W. (2008) IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis. Journal of Leukocyte Biology, 83(2), pp. 361-367. (doi:10.1189/jlb.0604352)

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Publisher's URL: http://dx.doi.org/10.1189/jlb.0604352

Abstract

Langerhans cells (LC) migrate rapidly from epidermis to lymph node following epicutaneous application of antigen. In this study, we have explored the role of IL-18, a cytokine with structural similarities to IL-1β, in murine LC migration and contact hypersensitivity (CHS), which to oxazolone (OX) and 2-4,dinitrofluorobenzene (DNFB) was suppressed significantly in IL-18 knockout (IL-18−/−) mice and could be rescued by local intradermal administration of IL-18 prior to sensitization, suggesting that the defect in these mice was in the afferent phase of CHS. To determine the effect of IL-18 on LC migration, mice were treated topically with OX or DNFB, and remaining LC numbers were assessed. A significant decline in remaining epidermal LC occurred in wild-type (WT) mice but did not occur in IL-18−/− mice. Sodium lauryl sulfate, a nonantigenic LC migratory stimulus, induced equivalent LC migration in IL-18−/− and WT mice. In IL-18−/− mice, IL-1β and TNF-α were equally able to mobilize LC from epidermis, indicating that migration in response to these cytokines is not dependent on IL-18 and suggesting that IL-18 acts upstream of these cytokines in the initiation of antigen-induced LC migration. Moreover, IL-1β but not IL-18 was able to rescue the defective CHS response observed in caspase-1−/− mice, which have no functional IL-1β or IL-18. These data indicate that IL-18 is a key proximal mediator of LC migration and CHS, acting upstream of IL-1β and TNF-α, and may play a central role in regulation of cutaneous immune responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo
Authors: Antonopoulos, C., Cumberbatch, M., Mee, J. B., Dearman, R. J., Wei, X.-Q., Liew, F. Y., Kimber, I., and Groves, R. W.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Leukocyte Biology
Publisher:Federation of American Societies for Experimental Biology
ISSN:0741-5400
ISSN (Online):1938-3673
Published Online:05 November 2007
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
380241Toll-like receptors on T cellsFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine