Transcriptome Analysis of Desquamative Interstitial Pneumonia (DIP) [article]

Shigeki Saito, Jay K Kolls, Yaozhong Liu, Yusuke Higashi, Shinya Ohkouchi, Yasuhiro Kondoh, Joseph Lasky, Takuji Suzuki
2019 bioRxiv   pre-print
Desquamative interstitial pneumonia (DIP) is a rare diffuse parenchymal lung disease of unclear etiology. A recent study showed that mice overexpressing Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) in lungs develop DIP-like disease, suggesting that pulmonary GM-CSF may be involved in the pathogenesis of DIP. To determine if GM-CSF is involved in human DIP lungs, we performed transcriptome analysis on human DIP lung tissue. We also extended transcriptome analysis to respiratory
more » ... hitis - interstitial lung diseases (RB-ILD), which has been thought to be in the same spectrum of the disease process. The analysis revealed that DIP has a distinct transcriptome profile compared to both RB-ILD and non-diseased lung control. It also suggested that GM-CSF was a key upstream regulator in the DIP transcriptome and that the GM-CSF signaling pathway was highly activated in DIP tissue. Further bioinformatics analysis using xCell, a novel computational method that assesses enrichments of individual cell types based on gene expression, suggested that DIP is enriched for gene signatures of macrophages and other immune cells such as dendritic cells and B cells. In conclusion, our analysis shows that DIP is characterized by a GM-CSF signature and thus, GM-CSF is likely to be involved in the pathogenesis of DIP. Our analysis also suggests that immune cells other than alveolar macrophages, such as B cells, may also be involved in the pathogenesis of DIP.
doi:10.1101/791350 fatcat:gptnls2rnzgr5bhl5n3ingrtfm