Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma

Abstract

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

The epithelial barrier theory: development and exacerbation of allergic and other chronic inflammatory diseases

“…Together with genetic background and environmental influences, epithelial barrier defect was highlighted to underlie the etiology of these disorders [ 3 – 5 ]. The discovery of the activated T-lymphocyte-mediated keratinocyte apoptosis in atopic dermatitis (AD) was the initial evidence to focus the research on epithelial barrier [ 4 , 6 ], which was consequently followed by demonstration of the epithelial barrier disruption in asthma, chronic rhinosinusitis (CRS), and inflammatory bowel disease (IBD) [ 7 – 9 ]. The mucosal barrier’s “keep away, wash away and suppress” functions are delicately facilitated by the immune system and encompass tissue and cell-related mechanisms.…”

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms

“…The available data still seems insufficient, and additional research is needed to complete and confirm the role of specific genes, identify biomarkers of CRS or even find causal relationships [ 3 , 15 ]. Common pathways of T2 inflammation in asthma or atopic dermatitis may help identify cardinal processes [ 16 , 17 ]. Rigorous study design in a clear-cut phenotype is a prerequisite to successfully interpreting big data in any genetic study [ 2 , 18 ].…”

Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment

“…In particular, topically active corticosteroids, antihistamines and mast cell stabilizers applied on nasal or conjunctival epithelium are widely used ( 14 – 16 ). In parallel, strategies to prevent loss of epithelial barrier integrity and to eventually avoid allergen entry have been pursued with great effort ( 17 , 18 ). The application of nasal filters to stop or at least reduce inhalation of pollen grains has also been reported, and such devices are recommended as supplements to, but not substitutes for pharmacological measures ( 19 , 20 ).…”