Author:
Khatri Aaditya,Kraft Bryan D.,Tata Purushothama Rao,Randell Scott H.,Piantadosi Claude A.,Pendergast Ann Marie
Abstract
Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections.
Funder
HHS | NIH | National Heart, Lung, and Blood Institute
HHS | NIH | National Institute of General Medical Sciences
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
Cystic Fibrosis Foundation
HHS | NIH | National Cancer Institute
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
Proceedings of the National Academy of Sciences
Cited by
13 articles.
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