Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0604352 on November 5, 2007

Published online before print November 5, 2007
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
jlb.0604352v1
83/2/361    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Antonopoulos, C.
Right arrow Articles by Groves, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Antonopoulos, C.
Right arrow Articles by Groves, R. W.
(Journal of Leukocyte Biology. 2008;83:361-367.)
© 2008 by Society for Leukocyte Biology

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

Christos Antonopoulos*, Marie Cumberbatch{dagger}, John B. Mee*, Rebecca J. Dearman{dagger}, Xiao-Qing Wei{ddagger}, Foo Y. Liew§, Ian Kimber{dagger} and Richard W. Groves*,1

* St. John’s Institute of Dermatology, King’s College London, London, United Kingdom;
{dagger} Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom;
{ddagger} School of Dentistry, Cardiff University, Cardiff, United Kingdom; and
§ Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom

1 Correspondence: St. John’s Institute of Dermatology, Guy’s Hospital, St. Thomas Street, London, SE1 9RT, UK. E-mail: richard.groves{at}kcl.ac.uk

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-{alpha} 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-{alpha}, and may play a central role in regulation of cutaneous immune responses.

Key Words: oxazolone • lymph nodes • caspase-1




This article has been cited by other articles:


Home page
 Toxicol SciHome page
A. Natsch
The Nrf2-Keap1-ARE Toxicity Pathway as a Cellular Sensor for Skin Sensitizers--Functional Relevance and a Hypothesis on Innate Reactions to Skin Sensitizers
Toxicol. Sci., February 1, 2010; 113(2): 284 - 292.
[Abstract] [Full Text] [PDF]