Mucosal immune barrier and antigen-presenting system in human nasal epithelial cells

The upper respiratory tract including the nasal cavity, which is the first site of invading antigen exposure, plays a crucial role in host defense via the mucosal immune response. The epithelium of nasal mucosa forms a continuous barrier against a wide variety of exogenous antigens. The epithelial barrier function is regulated in large part by the apical-most intercellular junction, referred to as the tight junction. Antigen-presenting cells, particularly dendritic cells (DCs), are known to play an important role in human nasal mucosa. Recently, the author and colleagues discovered a new mechanism for pathogen uptake in the nasal mucosa, by which DCs open the tight junctions between epithelial cells and send dendrites outside the epithelium to directly sample the pathogen. In order to preserve the integrity of the epithelial barrier and penetrate beyond well-developed epithelial tight junctions, DCs express tight junction proteins. We also found that these DCs are activated by nasal epithelial-derived TSLP induced by stimuli such as cytokines and Toll-like receptor ligands. In this lecture, I will talk about the novel mechanisms in host defense in terms of innate immunity of the nasal mucosa from the point of view of the mucosal barrier function.