Figure 1.

Upon allergen proteases exposure, junctional proteins among epithelial cells are disrupted. Allergen proteases can directly react with protease-activated receptor 2 (PAR2). Allergen proteases cleave the serum factor fibrinogen, thus releasing fibrinogen cleavage products (FCPs) which can activate toll-like receptor 4 (TLR4). Epithelial cells get activated to produce and release pro-Th2 cell chemokines and cytokines which instruct immature dendritic cells (iDC) and activate ILC2s. Additionally, the activation of these receptors will also induce NF-kB activation, ROS production. Th2 cells and ILC2s are activated and promote the eosinophilia, production of IgE and goblet-cell metaplasia. Allergen exposure is generally accompanied by fluid extravasation and thrombin also generates FCPs from fibrinogen, thus triggering TLR4. P-glycoproteins (P-gp) in the epithelial cells promote the efflux of protease inhibitors to suppress the allergen proteases. cDC classical DC, Macro macrophage, Baso basophils, MC mast cell.