title: Cellular mechanisms of alveolar pathology in childhood interstitial lung diseases: current insights from mouse genetics.
abstract: OBJECTIVE
  Childhood interstitial lung diseases (ILDs) are a diverse class of disorders affecting the alveolar gas exchange region that lack specific treatments and are usually fatal. Here, we integrate recent insights into alveolar cell biology with histopathology from well characterized mutations of surfactant-associated genes. We take a reductionist approach by parsing discrete histological features and correlating each to perturbation of a particular function of the alveolar epithelial type II (AT2) cell, the central driver of disease, to generate a working model for the cellular mechanisms of disease pathogenesis.
  
  
  RESULTS
  The application of genetically modified mice and single cell genomics has yielded new insights into lung biology, including the identification of a bipotent alveolar progenitor in development, mapping of adult AT2 stem cells in vivo, and demonstration that latent cooperative interactions with fibroblasts can be pathologically activated by targeted injury of the AT2 cell.
  
  
  CONCLUSIONS
  As we learn more about individual and cooperative roles for alveolar cells in health, we can dissect how perturbations of specific cellular functions contribute to disease in childhood ILDs. We hope our updated model centered around the AT2 cell as the initiator of disease provides a cellular framework that researchers can build upon and revise as they identify the specific molecular signals within and between alveolar cells that mediate the diverse pathologic features, so that targeted pharmacologic and cell-based treatments for patients can ultimately be engineered.
authors.affiliation: Department of Pediatrics, Division of Pediatric Pulmonary Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Christin S
authors.initials: CS
authors.lastname: Kuo
authors.forename: Tushar J
authors.initials: TJ
authors.lastname: Desai
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002648:Child; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000166:cytology / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000473:pathology*; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology*; D015398:Signal Transduction