Mechanisms and biomarkers of airway epithelial cell damage in asthma: A review

Abstract

Bronchial asthma, or asthma for short, is a chronic disease of the airway characterised by symptoms such as respiratory distress, chest tightness, wheezing, coughing, sputum formation and exercise intolerance. The asthmatic airway is chronically inflamed due to the activation and/or recruitment of a variety of tissue resident and infiltrating cells including eosinophils, mast cells, T lymphocytes, macrophages, airway epithelial cells (AECs), fibroblasts and airway smooth muscle (ASM) cells. The AEC, which sits at the interface between the host and the external environment, is not only an efficient physical barrier but also represents the first line of defence against microorganisms, airborne irritants and allergens. 1 The airway epithelium maintains the health of the respiratory tract mucosa through its physical barrier function, cilia removal function and natural immune defence function. It plays a central role in the pathogenesis of asthma. On the one hand, changes in its structure and function directly affect the inflammatory response and promote disease formation. On the other hand, the airway epithelium is also significantly damaged by inflammation. At present, the epithelial barrier has been placed in the forefront of the pathophysiology of airway inflammation. Epigenetic studies have confirmed that

Integrative Analysis Reveals a miRNA-mRNA Regulatory Network and Potential Causative Agents in the Asthmatic Airway Epithelium

“…14 However, the mechanisms underlying the airway epithelial cell dysfunction in asthma remain largely unknown. 15 The discovery of miRNA in 1993 16 made it possible to obtain a more comprehensive understanding of the asthma pathophysiology.…”

Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma

“…Asthmatic patients generally manifest different levels of chronic airway inflammation with airway epithelial damage that occurs even in mild, early and nonfatal asthma (110,111). Damage and shedding of airway epithelial cells are important pathological features of asthma, and altered epithelium in the airway is more susceptible to injury and apoptosis than those from nonasthmatic individuals (112).…”

“…Specifically, epithelial cells derived from asthmatic patients collected by bronchial brushing seem to be more hyperreactive and less viable (113), which likely results from inflammatory damage. Furthermore, the airway of asthmatic patients is characterized by the dysregulation of airway epithelial repair, leading to a chronic cycle of wound repair coupled with bronchial remodeling (110).…”

Epithelial Autoantigen-Specific IgG Antibody Enhances Eosinophil Extracellular Trap Formation in Severe Asthma

“… 6 7 Many factors have been shown to contribute to a thickened epithelium, which provides a microenvironment for persistent airway inflammation. 8 9 Moreover, the bronchial epithelium is more susceptible to apoptosis, and activated caspases could contribute to the cleavage of structural proteins. 10 11 12 Regarding autoimmune mechanisms, the existence of epithelial cell-derived autoantigens, including cytokeratin (CK), and the pathogenic role of circulating autoantibodies to epithelial antigens have been identified in patients with nonallergic asthma, contributing to poor clinical outcomes.…”