Department of Pulmonary Disease, Qianfoshan Hospital, Shandong University, No. 16766 by 10 Run Road, Jinan, Shandong, 250014, China.
Inflammation. 2014 Aug;37(4):1070-7. doi: 10.1007/s10753-014-9830-4.
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.
变应性哮喘是由于过敏原引起的免疫炎症反应失调而引起的，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 细胞因子家族的一员，已被牵连诱导气道上皮细胞中的 Th2 细胞依赖性炎症，并且 IL-25 缺陷型小鼠表现出受损的 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。在这项研究中，我们使用卵清蛋白 (OVA) 致敏和攻击来诱导小鼠哮喘模型，并通过肺组织的组织学分析和总血清和 OVA 特异性免疫球蛋白 (Ig)-E 水平来证实。通过定量实时 PCR 和免疫组织化学分别检测 IL-25 的表达，通过流式细胞术检测支气管肺泡灌洗液 (BALF) 中 CD80 和 CD86 的水平来检测树突状细胞 (DC) 的激活。OVA 致敏和攻击的小鼠在肺中均显示出 IL-25 在 mRNA 和蛋白质水平上的高表达。我们还检测到 BALF 中 CD80 和 CD86 的表达也增加。在 BALF 中鉴定出 IL-25 mRNA 与其他 Th2 细胞产生的细胞因子（如 IL-4、IL-5 和 IL-13）之间存在紧密的相关性。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著减少。在这项研究中，我们表明 IL-25 促进了共刺激分子 CD80 和 CD86 在 DC 上的积累，然后诱导初始 CD4(+) T 细胞分化为促炎性 Th2 细胞，并促进 OVA 诱导的气道炎症中的 Th2 细胞因子反应。IL-25 促进 DC 群体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，并提出了一种以前未被认识的先天免疫途径，该途径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 的促进作用，并为哮喘的治疗提供一种有前途的策略。
