Ritchie Andrew I, Jackson David J, Edwards Michael R, Johnston Sebastian L
1 Airway Disease Infection Section, National Heart and Lung Institute, Imperial College, London, United Kingdom.
2 Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
Ann Am Thorac Soc. 2016 Mar;13 Suppl 1:S55-63. doi: 10.1513/AnnalsATS.201507-421MG.
Asthma is a very common respiratory condition with a worldwide prevalence predicted to increase. There are significant differences in airway epithelial responses in asthma that are of particular interest during exacerbations. Preventing exacerbations is a primary aim when treating asthma because they often necessitate unscheduled healthcare visits and hospitalizations and are a significant cause of morbidity and mortality. The most common cause of asthma exacerbations is a respiratory virus infection, of which the most likely type is rhinovirus infection. This article focuses on the role played by the epithelium in orchestrating the innate immune responses to respiratory virus infection. Recent studies show impaired bronchial epithelial cell innate antiviral immune responses, as well as augmentation of a pro-Th2 response characterized by the epithelial-derived cytokines IL-25 and IL-33, crucial in maintaining the Th2 cytokine response to virus infection in asthma. A better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to highlight current knowledge regarding the role of viruses and immune modulation in the asthmatic epithelium and to discuss exciting areas for future research and novel treatments.
哮喘是一种非常常见的呼吸道疾病,预计其全球患病率将会上升。哮喘患者气道上皮反应存在显著差异,在病情加重期间尤其值得关注。预防病情加重是治疗哮喘的主要目标,因为病情加重常常需要进行非计划的医疗就诊和住院治疗,并且是发病和死亡的重要原因。哮喘病情加重的最常见原因是呼吸道病毒感染,其中最可能的类型是鼻病毒感染。本文重点关注上皮细胞在协调对呼吸道病毒感染的固有免疫反应中所起的作用。最近的研究表明,支气管上皮细胞的固有抗病毒免疫反应受损,同时以上皮来源的细胞因子白细胞介素-25和白细胞介素-33为特征的辅助性T细胞2型(Th2)反应增强,这对于维持哮喘中Th2细胞因子对病毒感染的反应至关重要。更好地理解这些异常免疫反应的机制有可能促成针对病毒诱发病情加重的新型治疗靶点的开发。本文的目的是强调关于病毒和免疫调节在哮喘上皮细胞中的作用的现有知识,并讨论未来研究和新型治疗的令人兴奋的领域。