IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice
IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice
复制标题
DOI：
10.1016/j.jaci.2006.04.051
复制
发表时间：
2006-09-01
影响因子：
14.2
通讯作者：
Nakajima, Hiroshi
中科院分区：
文献类型：
--
作者：
Tamachi, Tomohiro;Maezawa, Yuko;Nakajima, Hiroshi
背景：一种新的IL-17家族细胞因子IL-25已被报道可诱导未定义的非T/非b细胞产生IL-4、IL-5和IL-13，然后诱导T(H)2型免疫反应。然而，IL-25在过敏性气道炎症诱导中的作用尚不清楚。目的：我们试图确定IL-25是否参与引起过敏性气道炎症。方法：检测吸入抗原致敏小鼠肺组织中il - 25mrna的表达。我们还研究了可溶性IL-25受体中和IL-25对抗原诱导的气道炎症的影响。然后，我们在Clara细胞-10-kd蛋白启动子的控制下，培养了IL-25转基因小鼠，在肺中特异性表达IL-25，并研究了IL-25的强化表达对抗原诱导的气道炎症的影响。结果：吸入抗原致敏小鼠肺中表达IL-25 mRNA，可溶性IL-25受体中和IL-25可减少抗原诱导的嗜酸性粒细胞和CD4(+) t细胞向气道募集。IL-25在肺内的强制表达不能诱导过敏性气道炎症，而IL-25的表达可显著增强抗原诱导的T(H)2细胞因子的产生、气道内嗜酸性粒细胞和CD4(+) T细胞的募集以及杯状细胞的增生。此外，il -25诱导的变应性气道炎症的增强被CD4(+) T细胞的消耗或信号换能器和转录激活因子的缺失所抑制。结论：IL-25通过扩增T(H)2细胞依赖性通路增强抗原诱导的变应性气道炎症。临床意义：IL-25可能参与T(H)2细胞介导的过敏性疾病（如哮喘）的增强、延长或两者兼而有之。
Background: A novel IL-17 family cytokine, IL-25, has been reported to induce IL-4, IL-5, and IL-13 production from undefined non-T/non-B cells and then induce T(H)2-type immune responses. However, the roles of IL-25 in inducing allergic airway inflammation remain unknown.Objective: We sought to determine whether IL-25 is involved in causing allergic airway inflammation.Methods: We examined the expression of IL-25 mRNA in the lungs of sensitized mice on antigen inhalation. We also examined the effect of IL-25 neutralization by soluble IL-25 receptor on antigen-induced airway inflammation. We then generated IL-25 transgenic mice that express IL-25 specifically in the lung under the control of the Clara cells-10-kd protein promoter and investigated the effect of enforced IL-25 expression on antigen-induced airway inflammation.Results: IL-25 mRNA was expressed in the lungs of sensitized mice on antigen inhalation, and the neutralization of IL-25 by soluble IL-25 receptor decreased antigen-induced eosinophil and CD4(+) T-cell recruitment into the airways. The enforced expression of IL-25 in the lung itself failed to induce allergic airway inflammation, whereas the expression of IL-25 significantly enhanced antigen-induced T(H)2 cytokine production, eosinophil and CD4(+) T cell recruitment, and goblet cell hyperplasia in the airways. Moreover, IL-25-induced enhancement of allergic airway inflammation was inhibited by the depletion of CD4(+) T cells or by the absence of signal transducer and activator of transcription 6.Conclusion: IL-25 enhances antigen-induced allergic airway inflammation by amplifying a T(H)2 cell-dependent pathway. Clinical implications: IL-25 might be involved in the enhancement, prolongation, or both of T(H)2 cell-mediated allergic diseases, such as asthma.