LAUSR

ABSTRACT Nasal epithelial cells are the first barrier against allergen infiltration in allergic rhinitis (AR), and the relationship between nasal epithelial cells and mast cell-mediated hypersensitivity remains unclear. This study aimed to investigate the possible association between allergen-challenged nasal epithelial cells (AR-HNEpC) and mast cell degranulation in AR. Our data revealed that calcium influx and degranulation were increased in AR-HNEpC-co-cultured mast cells. Expression of IL-33, a factor that binds to ST2 receptors on mast cells and regulates their degranulation, was elevated in AR-HNEpC. Blocking IL-33/ST2 pathway activated autophagy and inhibited degranulation and inflammatory factor release in mast cells. Furthermore, PI3K/mTOR was increased in IL-33-treated mast cells. Inhibition on PI3K/mTOR pathway enhanced autophagy and inhibited degranulation. Analysis using an in vivo AR model supported the above findings. In conclusion, IL-33 from epithelial cells promotes degranulation of mast cells in AR through inhibition on ST2/PI3K/mTOR-mediated autophagy, which provides a potential therapeutic target for the disease. Abbreviations: AR: allergic rhinitis; IL: interleukin; TNF-α: tumor necrosis factor-alpha; INF-γ: interferon-gamma; HNEpC: human nasal epithelial cell line; ATCC: American Type Culture Collection; C48/80: compound 48/80; 3-MA: 3-methyladenine; qPCR: quantitative PCR; AR-HNEpC: dust mite allergen-treated nasal epithelial cells; IgE: immunoglobulin E; Atg7: autophagy-related gene 7