Dual Role of Interleukin-23 in Epicutaneously-Sensitized Asthma in Mice
Dual Role of Interleukin-23 in Epicutaneously-Sensitized Asthma in Mice
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DOI：
10.2332/allergolint.13-oa-0632
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发表时间：
2014-05-10
影响因子：
6.8
通讯作者：
Asano, Koichiro
中科院分区：
文献类型：
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作者：
Masaki, Katsunori;Suzuki, Yusuke;Asano, Koichiro
背景：白细胞介素(IL)-23/Th17轴在哮喘和湿疹的病理生理中起重要作用，然而，关于该系统在过敏性气道炎症中的作用，有一些相互矛盾的数据。在本研究中，我们旨在剖析IL-23在小鼠表皮致敏哮喘模型中作用的时空差异。方法：先在C57BL/6小鼠皮肤上贴敷卵清蛋白（OVA），然后气道暴露于雾化的卵清蛋白。在致敏和/或激发阶段，腹腔注射针对IL-23的特异性中和抗体（Ab）或对照IgG。在最终暴露于OVA后的第1天和第8天，评估气道炎症和对甲胆碱的反应性、血清免疫球蛋白水平和脾细胞释放的细胞因子。应用定量RTPC r评估皮肤Il23a mRNA水平。结果：贴片应用时间依赖性地增加皮肤Il23a mRNA表达。与对照IgG治疗相比，在致敏期单独使用抗il -23 Ab治疗可显著降低过敏原攻击后支气管肺泡灌洗液和支气管周围间隙中嗜酸性粒细胞的数量。抗il -23 Ab也能降低ova特异性IgG的血清水平(1)。相反，在攻毒期单独使用抗il -23 Ab反而加重了气道对甲胆碱的高反应性，而对气道嗜酸性粒细胞或血清IgG(1)水平影响不大。结论：致敏期皮肤中表达的IL-23在过敏表型的发展中起重要作用，而挑战期气道中的IL-23则抑制气道的高反应性。
Background: Interleukin (IL)-23/Th17 axis plays an important role in the pathophysiology of asthma and eczema, however, there are some conflicting data about the effects of this system on allergic airway inflammation. In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an epicutaneously-sensitized asthma model of mice.Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway exposure to aerosolized OVA. During sensitization and/or challenge phase, either a specific neutralizing antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RTPC R.Results: Patch application time-dependently increased the expression of Il23a mRNA expression in the skin. Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG(1). In contrast, treatment with the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine with little effects on airway eosinophilia or serum IgG(1) levels.Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.