Immunological and regenerative properties of lung stem cells

The human lung is subjected to inhaled harmful substances, including pathogens, pollutants, and allergens. Two abundant epithelial stem cell populations, the club cells and the alveolar type 2 (AT2) cells, are located in the airways and alveoli, respectively, and possess versatile properties including barrier repair, antimicrobial secretion, antigen presentation, as well as active communication with immune cells, to strengthen defense responses in the lung. In this review, we summarize challenges at the lung epithelium and update our current understanding of how lung stem cells respond to environmental insults that affect the lung epithelial barrier and their importance for host defense. Active cross talk between lung stem cells and immune cells is then discussed. We also consider how dysregulations of these stem cells contribute to pathological conditions affecting the lung, including acute infections, chronic progressions, and tumor development. Proper repopulation and functional restoration of these cells may represent a novel therapeutic strategy for treating intractable lung diseases associated with barrier disruption and immune imbalance.