ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia

Significance Approximately 50,000 cases ofStaphylococcus aureus pneumonia occur each year. These infections are associated with high mortality rates and frequently progress to multiorgan system failure. Treatment is limited to antibiotics and supportive care. Here we show that Abl kinase inhibition enhances proliferation and differentiation of a subpopulation of lung epithelial cells following pathogen-induced lung injury. We found that a subset of secretory cells in the lower airway expands to sites of injury in the alveolar epithelium to promote regeneration. Mice treated with an Abl kinase inhibitor recovered faster than vehicle control-treated mice following pathogen-induced lung injury. Therapeutic strategies to promote lung epithelial cell regeneration after injury could profoundly improve patient outcomes when used in combination with antibiotics and supportive care.