Dose-dependent IL-29 activation of TLR4 signalling drives eosinophil infiltration in chronic rhinosinusitis with nasal polyps

Objective: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) features extensive eosinophil infiltration, yet the molecular mechanisms driving this process are not fully elucidated. IL-29 and TLR4 are known inflammatory modulators, but their dose-dependent interplay in ECRSwNP remains uncharted. This study aimed to explore how IL-29 activates TLR4 signalling to promote eosinophil infiltration in ECRSwNP.

Methods: Thirty patients with ECRSwNP and 30 controls post-nasal septum correction were recruited. Eosinophil infiltration was assessed via haematoxylin-eosin staining, while IL-29 and TLR4 expression and correlation were analysed using qPCR and immunohistochemistry. In vitro, eosinophils were stimulated with IL-29 (10-100 ng/mL) ± TLR4 Inhibitor TAK-242, with migration measured by Transwell assay, cytokine secretion by ELISA, and NF-κB/MAPK signalling by western blot.

Results: Patients with ECRSwNP exhibited significantly elevated eosinophil infiltration and IL-29/TLR4 expression (p < 0.05), with a robust correlation (r = 0.6018, p < 0.0001). IL-29 dose-dependently enhanced eosinophil migration and cytokine production, and the effects were reversed by TLR4 blockade, accompanied by decreased NF-κB and MAPK phosphorylation, indicating TLR4-mediated regulation.

Conclusions: Dose-dependent IL-29 activation of TLR4 signalling drives eosinophil infiltration in ECRSwNP, offering novel mechanistic insights and potential therapeutic targets for this condition.