Fig. 1.

Potential mechanism for amplification of type 2 inflammation in eosinophilic CRSwNP. Several factors including fungi, proteases, S. aureus, bacteria, viruses and allergens can activate nasal epithelial cells to induce the production of epithelial derived cytokines TSLP, IL-33 and IL-1. Epithelial derived cytokines activate three types of immune cells in NPs. TSLP stimulates mDCs to induce naive CD4⁺ T cell differentiation into Th2 cells which then induce adaptive type 2 inflammation. TSLP and IL-33 stimulate ILC2s to induce the production of type 2 cytokines (innate type 2 inflammation). Mast cells are accumulated in the epithelium and are also present in the mucosal area in NPs. TSLP, IL-33 and IL-1 stimulate epithelial and mucosal mast cells to produce IL-5 and IL-13 (innate type 2 inflammation). Ag/IgE/IgER complexes on mast cells induce degranulation and thereafter mast cells produce IL-5 and IL-13 (adaptive type 2 inflammation). Production of PGD2 and LTC4 from mast cells also stimulates ILC2s. IL-5 promotes eosinophilia and eosinophils produce CCL23 to recruit macrophages and mDC. IL-4/13 activates macrophages, B cells and epithelial cells to induce eosinophil and Th2 cell recruitment, remodeling and IgE mediated reactions. M2 macrophages produce eotaxins and CCL18 to recruit eosinophils, mDCs and Th2 cells.