IL-25: Regulator of Type 2 Inflammation in Allergic Nasal Mucosa

Abstract

Allergic nasal mucosal inflammation generally refers to the development of allergic rhinitis characterized by IgE-mediated mast cell responses, eosinophil infiltration, and augmented Th2 cytokines/chemokine production in the nasal mucosa. However, due to the complexity of the disease, its detailed mechanism has yet to be fully elucidated. Hence, in this review, we aim to collate the studies of IL-25 pertaining to its role in allergic mucosal inflammation to help drive future research of IL-25 in utilizing it as a potential target in the management of allergic sinonasal diseases. At the turn of the century, interleukin (IL)-25 was discovered as a novel member of the IL-17 cytokine family found to be derived mainly from nasal/airway epithelial cells, Th2 cells, and activated eosinophils. It is found to play a pivotal role in nasal allergic mucosal inflammation as a master regulator of promoting type 2 responses mediated by both Th2 cells and ILC2s, augmenting allergic inflammation. IL-25 is highly bioactive by mainly reacting through IL-25R/IL-17RB which activates a myriad of transcriptional factors including p38 MAPK, NF-κB, STAT 5, and Act1 which contributes to its role in allergic mucosal inflammation. This review collated results that showed that IL-25 serves as a bridge between the epithelial cells and inflammatory cells in the sinonasal mucosa in promoting type 2 allergic inflammation, as well as between the innate immunity and acquired immunity via the feedback between ILC2s and Th2 cells to amplify and perpetuate allergic inflammation, which indicates IL-25 as a promising target for future biologics development.