Abstract
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.
Highlights
Affecting more than 300 children and adults worldwide [1], asthma is a chronic inflammatory disease characterized by chest tightness, variable airflow limitation, coughing, wheezing and airway hyperresponsiveness to environmental triggers [2,3]
It is evident that the airway epithelium plays a key role in the initiation and orchestration of the immune response to various environmental factors. Inhaled agents such as aeroallergens, pollutants, and respiratory viruses are sensed by the airway epithelium via a diverse set of pattern recognition receptors (PRRs) like the toll-like receptors (TLRs), retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), C-type lectin receptors (CLRs), and protease-activated receptor (PAR)
By using a human experimental model of RV exacerbation, Jackson et al found that subjects with asthma had increased levels of IL-33 and that this correlated with the type 2 (T2) cytokines IL-5 and IL-13 in the airway lining fluid as well as exacerbation severity after virus inoculation [121]
Summary
Affecting more than 300 children and adults worldwide [1], asthma is a chronic inflammatory disease characterized by chest tightness, variable airflow limitation, coughing, wheezing and airway hyperresponsiveness to environmental triggers (i.e., allergens, pollen, animal dander, tobacco smoke and air pollution) [2,3]. In the sensitization phase, inhaled allergens are captured by dendritic cells (DCs) and presented to naive CD4+ T cells in the presence of coactivators, including epithelial-derived cytokines, which promotes activation and polarization of T helper 2 (Th2) cells that produce IL-4, IL-5, and IL-13 [3,4] These T2 cytokines are produced by type 2 innate lymphoid cells (ILC2s) and are prominent orchestrators of the allergic inflammatory cascade that occurs in asthma. Current knowledge of the underlying molecular mechanisms in in asthma subgroups is limited, and more information is needed in order to improve disease asthma subgroups is limited, regimes. The airway is the first lineand of defense against pathogenic environmental factors suchplays as allergens,epithelium pollution, viruses, fungi, bacterial infections [8]. Disease development and progression in asthma [8,9]
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