IFN-γ and YAP lead epithelial cells astray after severe respiratory infection.

Ineffective recovery from pneumonia can lead to interstitial lung disease characterized by aberrant epithelial cells in fibrotic regions. In this issue of the JCI, Lin et al. define molecular pathways leading to the development and persistence of keratin 5+ (Krt5+) epithelial cells in the alveolar parenchyma when mice struggle to recover from influenza infection. The receptor for IFN-γ on lung epithelium was essential for the formation of aberrant Krt5+ cells and fibrotic lung disease. The transcription factor Yes-associated protein 1 (YAP) was necessary for persistence of these Krt5+ cells, and IFN-γ activated YAP in lung epithelial cells via JAK, focal adhesion kinase (FAK), and Src kinases. These findings establish a targetable pathway underlying some of the pulmonary postacute sequelae of pneumonia.