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

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.

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.

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.

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