Epithelial Barrier in the Nasal Mucosa, Related Risk Factors and Diseases

Abstract

As the first line of defense against risk factors, the nasal epithelial barrier maintains homeostasis in nasal mucosa. The composition of the epithelial barrier contains physical, chemical, immune, and microbiological barriers. Together, these barriers form the nasal defense against irritations. Risk factors from both internal and external environments can disrupt them. External risk factors contain allergens containing proteases, bacteria, virus, particulate matter, diesel exhaust particles, and cigarette smoke. In the meantime, inflammatory cytokines also increase the load on the barrier. Taking into account the role of the epithelial barrier in the nasal mucosa, some studies focus on the treatment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) by restoring the epithelial barrier, and some progress has been made. Among the therapeutic approaches, histone deacetylase (HDAC) inhibitor and steroid corticosteroids are considered two of the more studied categories, and their roles in repairing barriers have been demonstrated in AR and CRS. The underlying mechanism of HDAC inhibitor may be related to the transcription factor p63. And the protection of corticosteroids may be associated with the allergic disease susceptibility gene, protocadherin-1. Notably, manipulation of the microbiological barrier also has a positive effect on AR and CRS. Lactococcus and probiotics are two categories that are worth being explored continuously. We here review and discuss the compositions and risk factors of the nasal epithelial barrier. Furthermore, some novel and promising approaches to restore the defective barrier in nasal allergic diseases were mentioned.

Keywords: Allergic rhinitis; Chemical barrier; Chronic rhinosinusitis; Epithelial barrier; Physical barrier; Risk factors; Tight junctions.

Fig. 1

Compositions of the nasal epithelial barrier, risk factors, and immune responses. Epithelial barrier consists of physical, chemical, immune, and microbiological barriers. The physical barrier is mainly composed of TJs and AJs. TJs contain OCLN, CLDNs, JAMs, and ZO. AJs include cadherin/catenin and nectin/afadin complexes. Mucus and cilia form the chemical barrier. Igs and defense molecules (AMPs and proteins) act as the immune barrier. The microbiological barrier refers to the microbiota that colonizes the nasal mucosa. When the epithelial barrier is disrupted by the risk factors, a series of immune responses occur. Differentiated Th2 cells release some inflammatory cytokines and lead to the production of allergen-specific IgE. EOS, mast cells, and basophils are activated and degranulated. The released cytokines and allergic mediators cause continuous damage to the barrier. CS, cigarette smoke; DC, dendritic cell; EOS, eosinophil; HDM, house dust mite; IFs, intermediate filaments; Ig, immunoglobulin; ILC2, group 2 innate lymphoid cell; JAMs, junction adhesion molecules; PM and DEP, particulate matter and diesel exhaust particle; TSLP, thymic stromal lymphopoietin; ZO, zonula occludens.