SGK1 enhances Th9 cell differentiation and airway inflammation through NF-κB signaling pathway in asthma

This study aimed to explore the effect of Sgk1 on Th9 differentiation and the underlying mechanism in asthma. The asthmatic mouse model induced by ovalbumin (OVA) and CD4(+)T cells which were cultured with TGF-beta, IL-2, IL-4, and anti-IFN-gamma were applied in vivo and in vitro, respectively. Flow cytometry, quantitative real-time PCR (qRT-PCR), and ELISA were performed to detect T-helper 9 (Th9) cells, IL-9 expression, and IL-9 release. Western blot was performed to examine phosphorylated(p)-IKK alpha, p-I kappa B alpha, p-p65, and IRF4 levels. Hematoxylin/eosin (H&E) staining was adopted to assess pathological changes of lung tissues. Inhibition of Sgk1 dramatically reversed elevated Th9 cells and IL-9 expression in the lung tissues of asthmatic mice. In vitro, Sgk1 promoted Th9 differentiation and elevated p-IKK alpha, p-I kappa B alpha, p-p65, and IRF4 levels, but inhibition of IKK alpha/I kappa B alpha/p65 pathway and IRF4 both reversed enhanced Th9 differentiation by Sgk1. Sgk1 -> IKK alpha/I kappa B alpha/NF-kappa Bp65 -> IRF4 -> Th9 axis may be implicated in asthma development.