Background/Aims

Neutrophilic inflammation is a common feature of chronic airway diseases and associated with corticosteroid resistance. The IL23-Th17 axis is a key contributor in airway neutrophilia. IL23 engages with IL23R and signals via TYK2 and JAK2 leading to Th17 polarization. IL17, a Th17 cytokine binds to its receptors on structural and immune cells resulting in neutrophil activation. Despite clinical reports suggesting elevated IL23 levels in serum of patients with neutrophilic inflammation, the direct effects of these cytokines on neutrophil function remain to be elucidated. We aim to study the potential role of the IL23-Th17 signaling pathway in neutrophilic airway diseases.

Results

Functional assays in neutrophils were performed. IL17 and IL23 increased ROS production. IL17 induced neutrophil migration, enhanced IL8-stimulated chemotaxis, and significantly increased CD11b surface expression. The expression of TYK2 and JAK2 was studied in peripheral blood immune cells of allergic and non-allergic donors. Non-allergic donors showed significantly higher expression of TYK2 and JAK2 compared to allergic donors. In vivo, we observed increased neutrophil counts in the BAL fluid of mice after intranasal application of IL23.

Conclusion

From our preliminary data, we conclude that IL17 and IL23 affect neutrophil functions. TYK2 and JAK2 are differentially expressed in immune cells from allergic donors compared to healthy controls. In further experiments, we plan to evaluate neutrophil function and TYK2/JAK-STAT expressions in samples from patients with neutrophilic airway diseases and study the effectiveness of TYK2/JAK inhibitors in vitro and in vivo.