Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 83, Issue 2, Pages 361-367Publisher
WILEY
DOI: 10.1189/jlb.0604352
Keywords
oxazolone; lymph nodes; caspase-1
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Funding
- Medical Research Council [G9818261] Funding Source: Medline
- MRC [G9818261] Funding Source: UKRI
- Medical Research Council [G9818261] Funding Source: researchfish
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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-1 beta, 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-1 beta 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-1 beta but not IL-18 was able to rescue the defective CHS response observed in caspase-1 -/- mice, which have no functional IL-1 beta or IL-18. These data indicate that IL-18 is a key proximal mediator of LC migration and CHS, acting upstream of IL-1 beta and TNF-alpha, and may play a central role in regulation of cutaneous immune responses.
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