Fig. 8. A plausible mechanism for the development of nonallergic eosinophilic asthma.
a Airway epithelial cells stimulated by high doses of IL-23. High-dose IL-23 binds to IL-23R and induces the secretion of IL-33, TSLP, and IL-1β from airway epithelial cells; these factors can activate ILC2s and ILC3s. Activated ILC2s and ILC3s cause eosinophilic airway inflammation and AHR. In addition, high-dose IL-23 contributes to the development of AHR by directly activating Th17 cells and neutrophils. b Airway epithelial cells stimulated by low doses of IL-23 plus nonspecific airway irritants (polyI:C or DEPs). Low-dose IL-23 plus nonspecific airway irritants induce the secretion of a small amount of IL-23 from airway epithelial cells and increases the expression of IL-23R on airway epithelial cells. The secreted IL-23 forms a positive autocrine loop by binding to the increased IL-23R, thereby inducing secretion of IL-33, TSLP, and IL-1β (as with the high-dose of IL-23). Activated ILC2s and ILC3s cause eosinophilic airway inflammation and AHR. ASMC airway smooth muscle cell; AHR airway hyperresponsiveness.