Key role of the epithelium in chronic upper airways diseases

Abstract

The respiratory epithelium of the upper airways is a first‐line defence against inhaled irritants, pathogens and allergens. It ensures a physical barrier provided by apical junctions and mucociliary clearance to avoid excessive activation of the immune system. The epithelium also forms a chemical and immunological barrier, extensively equipped to protect the airways against external aggressions before the adaptive immune system is required. Under normal circumstances, the epithelium is capable of recovering rapidly after damage. This manuscript reviews these main properties of the upper airway epithelium as well as its reported impairments in chronic inflammatory diseases. The knowledge on normal epithelial functions and their dysregulation in upper airway diseases should help to design new epithelial‐targeted treatments.

Epithelial barriers in allergy and asthma

“…The epithelium lining the nasal and bronchial mucosa has 3 major functions in maintaining a healthy state of the respiratory mucosa: that is, physical barrier function, innate immune defense function, and mucociliary clearance of inhaled particles. 1 These mechanisms aim to prevent inflammation and disease despite the inhalation of infectious agents, pollutants, or allergens. Most environmental molecules are trapped in the mucus layer of the host mucosa and are cleared from the surface by the continuous and coordinated ciliary movements.…”

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

“…The epithelium operates as a physical barrier and plays a critical role in fluid balance, immune response, and tissue repair [ 4 , 30 , 31 ]. Although the general function of the epithelium remains constant throughout the respiratory tract, the specific cellular composition is location-dependent: the epithelium transitions from pseudostratified, ciliated, columnar morphology present in the proximal regions of the conducting zone to simple cuboidal in the small airway, then into a simple squamous epithelium in the alveoli [ 32 ].…”

“…The apical surface of the epithelium is exposed to air and inhaled substances, while the basal surface is in contact with the underlying submucosa (ECM, interstitial cells, and vasculature). The unique air–liquid interface (ALI) present in the airways results in the epithelium acting as the first line of defense against inhaled particulates, toxins, and pathogens [ 4 , 5 ]. The complex architecture of the lung, including and especially the ALI, is challenging to replicate in vitro.…”

A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets

“…Approximately 250, 000 confirmed deaths are reported annually worldwide due to respiratory failure during asthma exacerbations (Christiansen and Zuraw, 2019). Airway epithelial cells play a pivotal role in asthma pathogenesis, including airway inflammation, mucus overproduction, airway wall remodeling, and bronchial hyperresponsiveness (Gohy et al, 2020;Hellings and Steelant, 2020;Hammad and Lambrecht, 2021). However, the intrinsic molecular mechanisms of epithelial cells in asthma are still not fully clarified.…”