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This video is adapted from 10.3390/cells11101593
Idiopathic lung fibrosis (IPF) is a fatal lung disease characterized by chronic epithelial injury and exhausted repair capacity of the alveolar compartment, associated with the expansion of cells with intermediate alveolar epithelial cell (AT2) characteristics. Using SftpcCreERT2/+: tdTomatoflox/flox mice, researchers previously identified a lung population of quiescent injury activated alveolar epithelial progenitors (IAAPs) marked by low expression of the AT2 lineage trace marker tdTomato (Tomlow), and characterized by high levels of Pd-l1 (Cd274) expression. This led researchers to hypothesize that a population with similar properties exists in the human lung. To that end, researchers used flow cytometry to characterize the CD274 cell surface expression in lung epithelial cells isolated from donor and end-stage IPF lungs. The identity and functional behavior of these cells were further characterized by qPCR analysis, in vitro organoid formation, and ex vivo precision-cut lung slices (PCLS). Their analysis led to the identification of a population of CD274pos cells expressing intermediate levels of SFTPC, which was expanded in IPF lungs. While donor CD274pos cells initiated clone formation, they did not expand significantly in 3D organoids in AT2-supportive conditions. However, an increased number of CD274pos cells was found in cultured PCLS. In conclusion, researchers demonstrate that, similar to the IAAPs in the mouse lung, a population of CD274 expressing cells exists in the normal human lung and this population is expanded in the IPF lung and in an ex vivo PCLS assay, suggestive of progenitor cell behavior.