The Airway Epithelium—A Central Player in Asthma Pathogenesis

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.

Extracellular Vesicles in Allergic Rhinitis and Asthma and Laboratory Possibilities for Their Assessment

“…The Th2 cells, by IL-4 and IL-13 acting in concert, support further production of IgE synthesis and, together with IL-5, induce local and systemic eosinophilia perpetuating inflammatory response. Furthermore, a Th2 response leads to the generation of IgE memory B cells [ 7 , 8 , 9 ].…”

Treatment Response Biomarkers in Asthma and COPD

“…Reduced barrier function in the respiratory epithelium seems to play an important role in T2-high asthma, as microbes and allergens activate epithelial-derived alarmins, such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 [ 10 ]. Activation of these upstream cytokines results in several type 2 immune responses.…”

Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma

“…Within this pathobiological context, the bronchial epithelium exerts pivotal functions by producing three innate cytokines named alarmins, which include thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25) [ 9 , 10 , 11 ]. The secretion of these cytokines occurs when airway epithelial cells undergo injuries caused by several environmental triggers such as allergens, respiratory viruses, bacteria, cigarette smoking, and airborne pollutants ( Figure 1 ) [ 12 ]. Therefore, TSLP, IL-33, and IL-25 provide alarm signals which solicit the immune system to react to bronchial epithelial damage [ 9 ].…”