Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

Recently, a critical role in the development of allergic rhinitis (AR) has been attributed to the nasal epithelium. The airway epithelium forms a physical barrier, protecting the nasal mucosa and underlying organs from damage from contact with exogenous particles. The nasal epithelial barrier is primarily determined by the integrity of the airway epithelium, in which epithelial cells are connected to each other by complex network structures like tight junctions (TJs), ultimately sealing off the paracellular space. TJs consist of different transmembrane proteins including occludin, tricellulin, the claudin family, and junctional adhesion molecules. TJ form intercellular homodimers/heterodimers between neighboring cells. Scaffold adaptor proteins like cingulin and the zonula occludens family connect the transmembrane proteins to the actin cytoskeleton. Disturbed TJ function can facilitate the entrance of foreign pathogens and antigens into the submucosal layer, giving raise to allergic sensitization via increased access of allergens to the dendritic cells and/or inducing persistent inflammation via activation of mast cells and other inflammatory cells residing in the upper airways. Chronic disorders like allergic asthma, inflammatory bowel disease and atopic dermatitis have been linked to defective or altered TJ function. Recently, an impaired epithelial barrier function was found in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), suggesting changes in TJ arrangement in the nasal cavity. CRSwNP presents a similar inflammation of the sinonasal cavities as found in AR patients, i.e. a Th2 cytokine driven inflammation with tissue eosinophilia. Nevertheless, the role of TJs and its regulation has not been investigated in AR.