Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection.
Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection.
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DOI：
10.1016/j.jaci.2012.07.031
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发表时间：
2012-11
影响因子：
14.2
通讯作者：
Ziegler, Steven F.
中科院分区：
文献类型：
--
作者：
Lee, Hai-Chon;Headley, Mark B.;Loo, Yueh-Ming;Berlin, Aaron;Gale, Michael, Jr.;Debley, Jason S.;Lukacs, Nicholas W.;Ziegler, Steven F.
呼吸道病毒感染，包括呼吸道合胞病毒（RSV）和鼻病毒，与儿科患者的呼吸道疾病有关，包括严重急性细支气管炎和哮喘加重。该研究检测了上皮源性细胞因子胸腺基质淋巴生成素（TSLP）在RSV感染应答中的作用。通过感染人气道上皮细胞检测RSV感染后TSLP的诱导情况。对健康儿童和哮喘儿童感染后的气液界面培养进行了TSLP生成检测。最后，采用小鼠模型直接检测TSLP信号在RSV感染应答中的作用。RSV感染气道上皮细胞通过激活维甲酸诱导基因I、干扰素启动子刺激因子1和核因子-κB等先天信号通路导致TSLP的产生。与这一观察结果一致，哮喘儿童呼吸道上皮细胞在RSV感染后产生的TSLP水平明显高于健康儿童。在小鼠模型中，rsv诱导的TSLP表达对免疫病理的发展至关重要。这些发现表明RSV可以利用先天抗病毒信号通路来驱动潜在的非生产性免疫反应，并且对TSLP在病毒免疫反应中的作用具有重要意义。
Respiratory viral infection, including respiratory syncytial virus (RSV) and rhinovirus, has been linked to respiratory disease in pediatric patients, including severe acute bronchiolitis and asthma exacerbation. The study examined the role of the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) in the response to RSV infection. Infection of human airway epithelial cells was used to examine TSLP induction after RSV infection. Air–liquid interface cultures from healthy children and children with asthma were also tested for TSLP production after infection. Finally, a mouse model was used to directly test the role of TSLP signaling in the response to RSV infection. Infection of airway epithelial cells with RSV led to the production of TSLP via activation of an innate signaling pathway that involved retinoic acid induced gene I, interferon promoter-stimulating factor 1, and nuclear factor-κB. Consistent with this observation, airway epithelial cells from asthmatic children a produced significantly greater levels of TSLP after RSV infection than cells from healthy children. In mouse models, RSV-induced TSLP expression was found to be critical for the development of immunopathology. These findings suggest that RSV can use an innate antiviral signaling pathway to drive a potentially nonproductive immune response and has important implications for the role of TSLP in viral immune responses in general.
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