Fig. 1.

Sources of ILC2 activation and downstream mediators. Upon exposure to environmental antigens including viruses and allergens, airway epithelial cells rapidly release cytokines IL-25, IL-33, and TSLP that directly activate ILC2s. Additionally, PGD₂ and CysLTs from activated mast cells and eosinophils, as well as TL1A produced by DCs, can potently activate ILC2s. Allergens induce CysLT and PGD₂ production from mast cells through binding of surface IgE. Activation of ILC2s results in the secretion of Th2 cytokines IL-5, IL-9, and IL-13. AREG is largely made by ILC2s after stimulation with IL-33, and IL-4 is produced by ILC2s after stimulation with CysLTs, PGD₂, and TSLP. These mediators can then influence other airway cells to induce adaptive Th2 cell differentiation, eosinophil recruitment and activation, AHR, mucus production, and tissue repair and remodeling. CysLT cysteinyl leukotrienes, PGD₂ prostaglandin D₂, AREG amphiregulin