IL-25 Promotes Th2 Immunity Responses in Airway Inflammation of Asthmatic Mice via Activation of Dendritic Cells
IL-25 Promotes Th2 Immunity Responses in Airway Inflammation of Asthmatic Mice via Activation of Dendritic Cells
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DOI：
10.1007/s10753-014-9830-4
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发表时间：
2014-02
期刊：
影响因子：
5.1
通讯作者：
Hong-jia Li;Caiqing Zhang;Lu Degan;L. Fen;Wang Chao;Jin-xiang Wu;Dong Liang
中科院分区：
文献类型：
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作者：
Hong-jia Li;Caiqing Zhang;Lu Degan;L. Fen;Wang Chao;Jin-xiang Wu;Dong Liang
过敏性哮喘是过敏原不适当的免疫炎症的结果，其特征是 Th2 适应性免疫反应。最近的研究表明，白细胞介素 (IL)-25（IL-17 细胞因子家族的成员）与诱导气道上皮 Th2 细胞依赖性炎症有关，而 IL-25 缺陷的小鼠表现出受损的 Th2 免疫反应；然而，这些细胞因子如何影响先天免疫反应仍知之甚少。在本研究中，我们使用卵清蛋白（OVA）致敏和激发来诱导小鼠哮喘模型，并通过肺组织的组织学分析以及总和OVA特异性免疫球蛋白（Ig）-E的血清水平进行证实。分别通过实时定量PCR和免疫组化检测IL-25的表达，流式细胞仪通过支气管肺泡灌洗液（BALF）中CD80和CD86的水平检测树突状细胞（DC）的活化。用 OVA 致敏和攻击的小鼠肺部的 mRNA 和蛋白质水平均显示出 IL-25 的高表达。我们检测到BALF中CD80和CD86的表达也增加。确定了 BALF 中 IL-25 mRNA 与产生细胞因子（例如 IL-4、IL-5 和 IL-13）的其他 Th2 细胞之间的紧密相关性。此外，当哮喘小鼠接受吸入皮质类固醇治疗时，炎症细胞浸润和炎症细胞因子分泌显着减少。在这项研究中，我们发现IL-25促进CD80和CD86共刺激分子在DC上的积累，然后诱导原始CD4+T细胞分化为促炎性Th2细胞，并在OVA诱导的气道炎症中促进Th2细胞因子反应。 IL-25 促进 DC 群激活和分化的能力被确定为 IL-17 细胞因子家族与先天免疫反应之间的联系，并表明了一种先前未被识别的先天免疫途径，可促进哮喘气道炎症中的 Th2 细胞因子反应。吸入皮质类固醇可能能够抑制 IL-25 的促进，并为哮喘治疗提供一种有前景的策略
Allergic asthma occurs as a consequence of inappropriate immunologic inflammation to allergens and characterized by Th2 adaptive immune response. Recent studies indicated that interleukin (IL)-25, a member of the IL-17 cytokine family, had been implicated in inducing Th2 cell-dependent inflammation in airway epithelium and IL-25-deficient mice exhibit impaired Th2 immunity responses; however, how these cytokines influence innate immune responses remains poorly understood. In this study, we used ovalbumin (OVA) sensitization and challenge to induce the murine asthmatic model and confirmed by histological analysis of lung tissues and serum levels of total and OVA-specific immunoglobulin (Ig)-E. The expression of IL-25 was detected by quantitative real-time PCR and immunohistochemistry, respectively, and the dendritic cells (DCs) activation was detected by levels of CD80 and CD86 in bronchoalveolar lavage fluid (BALF) by flow cytometry. The mice sensitized and challenged with OVA showed high expression of IL-25 in both mRNA and protein levels in lungs. We detected the expression of CD80 and CD86 in BALF was also increased. A tight correlation between IL-25 mRNA and other Th2 cells producing cytokines such as IL-4, IL-5, and IL-13 in BALF was identified. Furthermore, when the asthmatic mice were treated with inhaled corticosteroids, the inflammatory cells infiltration and the inflammatory cytokines secretion were significantly decreased. In this study, we show that IL-25 promoted the accumulation of co-stimulatory molecules of CD80 and CD86 on DCs and then induced the differentiation of prime naive CD4+T cells to become proinflammatory Th2 cells and promoted Th2 cytokine responses in OVA-induced airway inflammation. The ability of IL-25 to promote the activation and differentiation of DCs population was identified as a link between the IL-17 cytokine family and the innate immune response and suggested a previously unrecognized innate immune pathway that promotes Th2 cytokine responses in asthmatic airway inflammation. Inhaled corticosteroids might be capable of inhibiting the promotion of IL-25 and present a promising strategy for the treatment of asthma