The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development

Abstract

The respiratory epithelium constitutes the physical barrier between the human body and the environment, thus providing functional and immunological protection. It is often exposed to allergens, microbial substances, pathogens, pollutants, and environmental toxins, which lead to dysregulation of the epithelial barrier and result in the chronic inflammation seen in allergic diseases and asthma. This epithelial barrier dysfunction results from the disturbed tight junction formation, which are multi-protein subunits that promote cell-cell adhesion and barrier integrity. The increasing interest and evidence of the role of impaired epithelial barrier function in allergy and asthma highlight the need for innovative approaches that can provide new knowledge in this area. Here, we review and discuss the current role and mechanism of epithelial barrier dysfunction in developing allergic diseases and the effect of current allergy therapies on epithelial barrier restoration.

Allergic Airway Inflammation Emerges from Gut Inflammation and Leakage in Mouse Model of Asthma

“…Mouse model of asthma is characterized with AAI developed with i.p OVA sensitization and i.n challenge with OVA in BALB/c mice. This model is characterized by airway inflammation associated with increased type 2 lymphocytes infiltration, eosinophils, alveolar epithelial barrier damage, and mucus secretion by epithelial goblet cells, [2,15,16,32,33] however, the inflammatory manifestations in the gut in not well studied. As observed in several previous studies highlighted the importance of Th2 responses in both gut and lung, we first intend to observe the type of inflammation in the gut and lung at prechallenge and post-challenge conditions during the development of AAI in mouse model of asthma.…”

“…Type 2 inflammation is known to induce epithelial barrier damage in the gut and lungs. [16,[44][45][46] In UC, IL-13 is observed as a key effector cytokine in inducing intestinal epithelial barrier dysfunction promoting distinct pathogenesis of Th2-driven intestinal inflammation. [47,48] Previous observations in vitro showed epithelial apoptosis and reduced claudin expression mediated by STAT6-activated IL-13 in patients with UC.…”

Identification of Molecular Markers Related to Immune Infiltration in Patients with Severe Asthma: A Comprehensive Bioinformatics Analysis Based on the Human Bronchial Epithelial Transcriptome

“…Keratin, a member of fibrous structural proteins, can protect epithelial cells from stress and damage [ 27 ]. Disruption of epithelial barrier function, such as cornification or keratinization, might result in allergic diseases [ 28 ]. Inoue et al find that downregulation of epithelial defense genes and keratinization occurs in SA mouse sensitized by Alternaria [ 29 ].…”

Asthma and allergic diseases: Cross talk of immune system and environmental factors

“…Mucosal surface integrity and mucus secretion in the eye and nose, the upper respiratory tract, the gastrointestinal tract (GIT), and the urogenital tract are critical to impede diffusion and mediate elimination of invaded pollutants. Dysfunctional mucosal epithelial barriers have been associated with antigen invasion, inflammatory activation of epithelial cells, and allergic reactions leading to the development of allergic diseases [11,12]. The GIT that is exposed to the external environment through ingested particles taken up by diet, inhalation, or other interventions exhibits a barrier formed by tightly connected epithelial cells lined with mucus and microbiota.…”