IPF AT2 cells are stuck in transition and biophysically dysfunctional
Year: 2026
Type: preprint
Abstract: Idiopathic Pulmonary Fibrosis (IPF) is an incurable disease with extensive molecular, cellular, and organ level dysfunction. A major gap in IPF research is the lack of understanding of how short-term cellular behavior causes long-term tissue remodeling. By optimizing lung slices from explanted human lungs, we discovered foci of migratory non-canonical alveolar type 2 (AT2) cells in regions of established lung fibrosis and found that these cells are trapped in states of cellular transition that are driven by persistent developmental repair programs. Consistent with these biophysical behaviors, pharmacological activation of β-catenin reproduced persistent migration, whereas YAP activation restrained it. We conclude that imbalanced developmental programs drive AT2 cell motility and lesion heterogeneity, providing a mechanistic link between short-term cellular dynamics and slowly progressive fibrosis of IPF.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: MUC5B, a novel therapeutic target for Idiopathic Pulmonary Fibrosis (IPF), Preclinical Pulmonary Fibrosis, an opportune rare disease cohort, Genes and Transcripts that Interact with MUC5B in Pulmonary Fibrosis, MUC5B, a novel therapeutic target for Idiopathic Pulmonary Fibrosis (IPF), Mechanisms Regulating Lung Injury and Early Lung Fibrosis, Molecular Determinants of Usual Interstitial Pneumonia (UIP)
OpenAlex ID: W7129366439