Observations on IL-2-inducible tyrosine kinase expression and Th17/Treg cell ratio in hyperoxia-induced bronchopulmonary dysplasia in neonatal rats.

BACKGROUND

The pathogenesis of bronchopulmonary dysplasia (BPD) is not fully understood, and there is currently a lack of effective therapeutic options. The immune responses of Th17 and Treg cells are regulated by the IL-2-inducible tyrosine kinase (ITK) signaling pathway, and the Th17/Treg imbalance is involved in the development of many lung diseases. However, the expression of Itk and the presence of a Th17/Treg imbalance in BPD have not been reported previously.

METHODS

Neonatal Sprague-Dawley rats (<12h old) were randomly assigned to hyperoxic (n = 30) or air groups (n = 30). At postnatal days (PD) 1,4,7,10,14, body weights were measured; 6 lungs/group were collected for H&E staining, Itk mRNA (RT-qPCR) and protein (Western blot) assays. On PD14, 8 rats/group were evaluated for splenic Th17/Treg cell ratio (flow cytometry) and lung IL-17/IL-10 (ELISA).

RESULTS

Hyperoxic group showed lower weights at PD10-14 and reduced radial alveolar counts (PD4-14). Itk mRNA (PD4-14) and ITK protein (PD10-14) were downregulated. Splenic Th17 cells and Th17/Treg ratio increased, while Tregs decreased. Lung IL-17 was higher and IL-10 lower in hyperoxic group.

CONCLUSION

Diminution in IL-2-inducible tyrosine kinase and Th17/Treg imbalance in hyperoxia-induced bronchopulmonary dysplasia model in neonatal rats, but the causal relationship between the two still needs to be confirmed by intervention studies.