Details

Autor(en) / Beteiligte

• Antonopoulos, Christos
• Cumberbatch, Marie
• Mee, John B.
• Dearman, Rebecca J.
• Wei, Xiao‐Qing
• Liew, Foo Y.
• Kimber, Ian
• Groves, Richard W.

Titel

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

Ist Teil von

• Journal of leukocyte biology, 2008-02, Vol.83 (2), p.361-367

Ort / Verlag

United States: Society for Leukocyte Biology

Erscheinungsjahr

2008

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• 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.