IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis
IL-18 is a key proximal mediator of contact hypersensitivity and allergen-induced Langerhans cell migration in murine epidermis
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DOI：
10.1189/jlb.0604352
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发表时间：
2008-02-01
影响因子：
5.5
通讯作者：
Groves, Richard W.
中科院分区：
文献类型：
--
作者：
Antonopoulos, Christos;Cumberbatch, Marie;Groves, Richard W.
朗格汉斯细胞（LC）迁移迅速。在表皮应用抗原后从表皮到淋巴结。在本研究中，我们探讨了与IL-1 β结构相似的细胞因子IL-18在小鼠LC迁移和接触性超敏反应（CHS）中的作用，其中对恶唑酮（OX）和2-4，二硝基氟苯（DNFB）的接触性超敏反应在IL-18敲除后被显著抑制（IL-18（-/-））小鼠，并且可以通过在致敏之前局部皮内施用IL-18来拯救，这表明这些小鼠中的缺陷在CHS的传入阶段。为了确定IL-18对LC迁移的影响，用OX或DNFB局部处理小鼠，并评估剩余的LC数量。在野生型（WT）小鼠中，剩余表皮LC显著下降，但在IL-18（-/-）小鼠中未发生。十二烷基硫酸钠是一种非抗原性LC迁移刺激物，在IL-18-/-和WT小鼠中诱导了等效的LC迁移。在IL-18-/-小鼠中，IL-1 β和TNF-α同样能够从表皮动员LC，表明响应于这些细胞因子的迁移不依赖于IL-18，并表明IL-18在抗原诱导的LC迁移的起始中在这些细胞因子的上游起作用。此外，IL-1 β而不是IL-18能够挽救在没有功能性IL-1 β或IL-18的胱天蛋白酶-1-/-小鼠中观察到的缺陷性CHS应答。这些数据表明，IL-18是LC迁移和CHS的关键近端介质，作用于IL-1 β和TNF-α的上游，并且可能在皮肤免疫应答的调节中发挥核心作用。
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.