The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts
The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts
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DOI：
10.1016/j.jaci.2012.08.030
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发表时间：
2013-03-01
影响因子：
14.2
通讯作者：
Andrews, Allison-Lynn
中科院分区：
文献类型：
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作者：
Campbell-Harding, Gemma;Sawkins, Hannah;Andrews, Allison-Lynn
背景：IL-13是哮喘患者过敏性炎症的关键介质。我们之前已经证明，诱骗受体IL-13受体(IL-13R)α2可以减弱成纤维细胞对IL-13的反应。由于IL-13Rα2的表达可受II型干扰素-γ的调节，我们假设以I型干扰素表达为特征的先天抗病毒反应也可以诱导IL-13Rα2的表达。目的：我们试图通过双链RNA(DsRNA)诱导原代成纤维细胞的天然抗病毒反应，并检测IL-13Rα2的表达和功能。方法：原代培养的人成纤维细胞，取自健康或哮喘志愿者的支气管镜活检标本，用dsRNA激发。用实时荧光定量聚合酶链式反应检测IL-13Rα2mRNA的表达，用荧光激活细胞分选法检测细胞表面IL-13Rα2蛋白的表达。结果：干扰素-β直接作用于成纤维细胞后，IL-13Rα2表达上调，dsRNA可迅速诱导成纤维细胞表达干扰素-β，随后IL-13Rα2mRNA和细胞表面蛋白表达显著增加，这依赖于从头蛋白的合成。干扰素-α/β受体的中和抗体在dsRNA存在的情况下阻断了细胞表面IL-13Rα2的表达。用dsRNA预处理成纤维细胞可抑制IL-13刺激的嗜酸性粒细胞趋化因子的产生。然而，IL13Rα2中和抗体的存在恢复了IL-13刺激的dsRNA处理细胞的嗜酸性粒细胞趋化因子的产生。结论：干扰素-β诱导IL-13Rα2的表达，导致对IL-13的反应性抑制。这些数据提示T(H)1和T(H)2通路之间的相互作用，并指出IL-13Rα2在病毒感染期间对人支气管成纤维细胞的免疫调节作用。(《过敏与免疫杂志》2013；131：849-55。)
Background: IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) alpha 2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13R alpha 2 can be regulated by IFN-gamma, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13R alpha 2 expression.Objective: We sought to induce an innate antiviral response in primary fibroblasts using exposure to double-stranded RNA (dsRNA) and to examine the expression and function of IL-13R alpha 2.Methods: Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13R alpha 2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13R alpha 2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA.Results: Direct treatment with IFN-beta led to an upregulation of IL-13R alpha 2. Exposure to dsRNA rapidly induced IFN-beta mRNA in fibroblasts, and this was followed by significant induction of IL-13R alpha 2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-alpha/beta receptor blocked cell-surface expression of IL-13R alpha 2 in the presence of dsRNA. Pretreatment of fibroblasts with dsRNA led to attenuation of IL-13-stimulated eotaxin production. However, the presence of an IL13R alpha 2 neutralizing antibody restored IL-13-stimulated eotaxin production in dsRNA-treated cells.Conclusion: IFN-beta induces IL-13R alpha 2 expression, leading to a consequential suppression of responsiveness to IL-13. These data suggest cross-talk between T(H)1 and T(H)2 pathways and point to an immunomodulatory role for IL-13R alpha 2 in human bronchial fibroblasts during viral infection. (J Allergy Clin Immunol 2013; 131:849-55.)