Human alveolar epithelial progenitor cells revealed pathophysiological mechanisms of refractory pulmonary diseases

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We developed a novel technique of cell isolation from human lung tissue, using a combination of cell surface antigens. This novel method enables the isolation of different cellular components from normal and diseased lungs, and is capable of elucidating phenotypes specific to certain alveolar cell types indicative of lung disease. Then, we identified genes commonly or differentially expressed by alveolar type II (ATII)-like cells differentiated from progenitor cells and mature ATII cells isolated from human lung tissues. Furthermore, we compared the genes expressed in ATII cells obtained from chronic obstructive pulmonary disease (COPD) and non-COPD patients, and found that interferon-stimulated genes associated with antigen processing and presentation were enriched in COPD-ATII cells. Genes involved in cell cycle progression were upregulated in COPD-ATII cells and the number of ATII cells in COPD lungs were increased. We also found that ATII cells isolated from patients with pulmonary fibrosis demonstrated increased severity of 2009 pandemic influenza A virus infection. This cell-based pulmonology will open a new strategy to treat intractable pulmonary diseases.