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IFN-γ and YAP lead epithelial cells astray after severe respiratory infection
Bradley E. Hiller, Joseph P. Mizgerd
Bradley E. Hiller, Joseph P. Mizgerd
Published October 1, 2024
Citation Information: J Clin Invest. 2024;134(19):e185072. https://doi.org/10.1172/JCI185072.
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Commentary

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

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Abstract

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.

Authors

Bradley E. Hiller, Joseph P. Mizgerd

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Figure 1

IFN-γ signaling drives dysplastic Krt5+ cells after lung infection.

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IFN-γ signaling drives dysplastic Krt5+ cells after lung infection.
Lin ...
Lin et al. (10) revealed that SOX2+ airway progenitor cells require IFNGR1 expression following influenza A virus infection for the development of aberrant KRT5+ epithelial cells within the alveolar parenchyma and subsequent fibrotic lung disease. IFN-γ activates the YAP transcription factor in lung epithelial cells via JAK, FAK, and Src kinases. YAP in dysplastic, parenchymal KRT5+ epithelial cells is essential for their expansion and maintenance. TCR, T cell receptor.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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