EpCAM deficiency causes the inflammation of lungs due to the reduction of pIgR in airway epithelium.

BACKGROUND

Immune homeostasis of the tracheobronchial epithelium is essential to the defense against pathogens for the lung. EpCAM is localized in the tracheobronchial epithelium, but the function and mechanisms of it on regulating the immunity in the respiratory tract remain unclear.

METHODS

The lung tissues from the EpCAM-deficient and wild type (WT) mice at E18.5, P0 and P3 stages were analyzed. The H&E staining was performed to check the morphological and histological changes of the mutant lungs. The qRT-PCR, western blot and immunofluorescence technologies were used to compare the expression and activities of genes related to inflammatory factors, immune cells and inflammation-associated signal pathways in the lungs from WT and EpCAM−/− embryos and pups.

RESULTS

The morphological changes and injuries of the lungs from the P3 EpCAM-deficient pups were detected. Several genes related to inflammatory factors and immune cells were upregulated in the mutant lungs. Furthermore, the lung abundant matrix metalloproteinases, such as MMP3 and MM8, were increased and the MAPK signal pathways were hyperactivated in the lungs from EpCAM−/− mice. The pIgR and IgA were significantly downregulated in the lungs from EpCAM-deficient mice. Additionally, signaling pathways regulating pIgR transcription were substantially suppressed in the lung tissues from the EpCAM−/− mice.

CONCLUSIONS

These results demonstrated the association between the EpCAM deficiency, the hyperactivation of immune signal pathways and the downregulation of pIgR in the lungs of mice, and the regulation of the pIgR expression might be the important mechanism of EpCAM on maintaining the immune homeostasis of the tracheobronchial epithelium.