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

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.

Galectin-7 overexpression destroys airway epithelial barrier in transgenic mice

When the integrity of airway epithelium is destroyed,the ordered airway barrier no longer exists and increases sensitivity to viral infections and allergens,leading to the occurrence of airway inflammation such as asthma.Here,we found that galectin-7 transgenic(+)mice exhibited abnormal airway structures as embryos and after birth.These abnormalities included absent or substantially reduced pseudostratified columnar ciliated epithelium and increased monolayer cells with irregular arrangement and widening of intercellular spaces.Moreover,airway tissue from galectin-7 transgenic(+)mice showed evidence of impaired cell–cell junctions and decreased expression of zonula occludens-1(ZO-1)and E-cadherin.When treated with respiratory syncytial virus(RSV)or ovalbumin(OVA),galectin-7 transgenic(+)mice developed substantially increased bronchial epithelial detachment and apoptosis,airway smooth muscle and basement membrane thickening,and enhanced airway responsiveness.We found that Galectin-7 localized in the cytoplasm and nucleus of bronchial epithelial cells,and that increased apoptosis was mediated through mitochondrial release of cytochrome c and upregulated JNK1 activation and expression of caspase-3 in galectin-7 Tg(+)mice.These findings suggested that Galectin-7 causes airway structural defects and destroys airway epithelium barrier,which predispose the airways to RSV or OVA-induced epithelial apoptosis,injury,and other asthma responses.