β1 Integrin regulates adult lung alveolar epithelial cell inflammation
Year: 2019
Type: article
Abstract: Integrins, the extracellular matrix receptors that facilitate cell adhesion and migration, are necessary for organ morphogenesis; however, their role in maintaining adult tissue homeostasis is poorly understood. To define the functional importance of β1 integrin in adult mouse lung, we deleted it after completion of development in type 2 alveolar epithelial cells (AECs). Aged β1 integrin-deficient mice exhibited chronic obstructive pulmonary disease-like (COPD-like) pathology characterized by emphysema, lymphoid aggregates, and increased macrophage infiltration. These histopathological abnormalities were preceded by β1 integrin-deficient AEC dysfunction such as excessive ROS production and upregulation of NF-κB-dependent chemokines, including CCL2. Genetic deletion of the CCL2 receptor, Ccr2, in mice with β1 integrin-deficient type 2 AECs impaired recruitment of monocyte-derived macrophages and resulted in accelerated inflammation and severe premature emphysematous destruction. The lungs exhibited reduced AEC efferocytosis and excessive numbers of inflamed type 2 AECs, demonstrating the requirement for recruited monocytes/macrophages in limiting lung injury and remodeling in the setting of a chronically inflamed epithelium. These studies support a critical role for β1 integrin in alveolar homeostasis in the adult lung.
Source: JCI Insight
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: U.S. Department of Veterans Affairs, Francis Family Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1245004033, G1344704808, G136329918, G2019238319, G2399267237, G2532530556, G2620099149, G2754227203, Lamellar Body Biogenesis in Health and Disease, G3001962234, G3012062859, Vanderbilt Mouse Metabolic Phenotyping Center, G3141307551, G318902089, Midcareer Investigator Award in Patient-Oriented Research in Pediatric Rare Lung Diseases, Vanderbilt O'Brien Kidney Center, Matrix receptors in chronic kidney disease, G3973429141, G4015142707, Vanderbilt Mouse Metabolic Phenotyping Center, G4252985639, G5027978258, G5983583798, G640983826, G6455254051, G711058138, Mechanisms of Pulmonary Fibrosis in Hermansky-Pudlak Syndrome, G725763919, G7569165298, G7653599784, G781560405, G8062473023, G8296124364, Vanderbilt Clinical Oncology Research Career Development Award, Molecular and Cellular Basis for Digestive Diseases, Vanderbilt Diabetes Research Center, Core Grant in Vision Research
OpenAlex ID: W2997027860