Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
Int J Mol Sci. 2020 Nov 24;21(23):8907. doi: 10.3390/ijms21238907.
Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction in response to a wide range of exogenous stimuli. The airway epithelium is the first line of defense and plays an important role in initiating host defense and controlling immune responses. Indeed, increasing evidence indicates a range of abnormalities in various aspects of epithelial barrier function in asthma. A central part of this impairment is a disruption of the airway epithelial layer, allowing inhaled substances to pass more easily into the submucosa where they may interact with immune cells. Furthermore, many of the identified susceptibility genes for asthma are expressed in the airway epithelium. This review focuses on the biology of the airway epithelium in health and its pathobiology in asthma. We will specifically discuss external triggers such as allergens, viruses and alarmins and the effect of type 2 inflammatory responses on airway epithelial function in asthma. We will also discuss epigenetic mechanisms responding to external stimuli on the level of transcriptional and posttranscriptional regulation of gene expression, as well the airway epithelium as a potential treatment target in asthma.
哮喘是一种慢性炎症性气道疾病，其特征是对外源性刺激的广泛反应导致气流受限的可变性。气道上皮是第一道防线，在启动宿主防御和控制免疫反应方面发挥着重要作用。事实上，越来越多的证据表明哮喘患者在气道上皮屏障功能的各个方面存在一系列异常。这种损伤的一个核心部分是气道上皮层的破坏，使吸入的物质更容易进入粘膜下层，在那里它们可能与免疫细胞相互作用。此外，哮喘的许多已确定的易感基因都在气道上皮中表达。这篇综述重点介绍了健康状态下气道上皮的生物学特性及其在哮喘中的病理生物学。我们将特别讨论过敏原、病毒和警报素等外部触发因素，以及 2 型炎症反应对哮喘中气道上皮功能的影响。我们还将讨论针对基因表达的转录和转录后调控水平的对外界刺激的表观遗传机制，以及气道上皮作为哮喘潜在治疗靶点的作用。
