IL-5Rα-Mediated Signaling in Eosinophils May Contribute to the Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND AND

OBJECTIVES

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is characterized by type 2 inflammation, prominent eosinophil accumulation, and enhanced epithelial-mesenchymal transition (EMT). Although interleukin (IL)-5 plays a central role in eosinophil differentiation and activation, its involvement in driving EMT in human nasal epithelial cells (HNECs) remains unclear. This study investigated IL-5 receptor α (IL-5Rα)-mediated signaling and EMT profiles in ECRSwNP, aiming to determine whether IL-5-activated eosinophil-like cells promote EMT in HNECs.

METHODS

Nasal tissues from healthy controls, non-ECRSwNP patients, and ECRSwNP patients (n=12 per group) were analyzed using hematoxylin and eosin staining, quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blotting. HL-60 promyelocytic leukemia cells were differentiated into eosinophil-like cells and subsequently stimulated with IL-5. HNECs were cocultured with undifferentiated HL-60 cells, differentiated HL-60 cells, or IL-5-stimulated differentiated HL-60 cells using a Transwell system. Expression of EMT-related markers was assessed by Western blotting and immunofluorescence.

RESULTS

ECRSwNP tissues demonstrated markedly increased eosinophil infiltration, elevated IL-4 and IL-5 transcript levels, and significantly higher expression of IL-5Rα, phosphorylated Janus kinase 2 (JAK2), and phosphorylated signal transducer and activator of transcription 5 (STAT5) compared with controls and non-ECRSwNP tissues. EMT-associated changes, characterized by reduced E-cadherin and increased vimentin expression, were most pronounced in ECRSwNP. In vitro, IL-5 stimulation enhanced IL-5Rα expression, activated JAK2/STAT5 signaling, and increased secretion of eosinophil-associated mediators in differentiated HL-60 cells. Co-culture with IL-5-stimulated eosinophil-like cells induced EMT in HNECs, whereas unstimulated HL-60 cells exerted minimal effects.

CONCLUSION

IL-5Rα-mediated signaling is upregulated in ECRSwNP and may contribute to EMT through eosinophil-dependent mechanisms. IL-5-activated eosinophils promote EMT-related changes in HNECs, providing a mechanistic link between type 2 inflammation and epithelial remodeling. These findings suggest that IL-5Rα signaling may represent a potential therapeutic target for modulating tissue remodeling in ECRSwNP.