The Role of Interleukin-4 in Olfactory Epithelial Cells: A Preliminary In Vitro Study

Olfactory epithelium (OE) comprises diverse cell types, including olfactory sensory neurons, supporting cells, and basal stem cells. While interleukin (IL)-4 is a key mediator in type 2 inflammation, its regulatory role in OE remains unclear. The current study aimed to explore the role of IL-4 in olfactory epithelial cells. Using an olfactory epithelial organoid model, the impacts of IL-4 on different cell types were assessed by performing qPCR, immunofluorescence staining, and EdU incorporation assays. Calcium imaging was performed to assess the influence of IL-4 on olfactory sensory neurons (OSNs), while Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining was used to analyze mucin secretion in the organoids. IL-4 significantly promoted the proliferation of globular basal cells (GBCs) in basal cells, induced homeostasis of mature OSNs, and maintained the normal function of OE. However, IL-4 notably downregulated GAP43 expression in immature OSNs. Additionally, IL-4 enhanced mucin secretion in the OE. This study found that IL-4 promoted the differentiation of OE cells by stimulating the proliferation of GBCs and enhancing mucin secretion, while maintaining the normal function of mature olfactory neurons. Further clinical studies are needed to validate these results. This study revealed the role of IL-4 in OE, providing novel insights into the mechanisms of IL-4 in inflammatory conditions.