Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution
Racquel Domingo-Gonzalez,
Fabio Zanini,
Xibing Che,
Min Liu,
Robert C Jones,
Michael A Swift,
Stephen R Quake,
David N Cornfield,
Cristina M Alvira
Affiliations
Racquel Domingo-Gonzalez
Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, United States
Department of Bioengineering, Stanford University, Stanford, United States; Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia
Xibing Che
Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, United States; Division of Pulmonary, Asthma and Sleep Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
Min Liu
Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, United States
Department of Bioengineering, Stanford University, Stanford, United States; Chan Zuckerberg Biohub, San Francisco, United States; Department of Applied Physics, Stanford University, Stanford, United States
David N Cornfield
Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, United States; Division of Pulmonary, Asthma and Sleep Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
Division of Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, United States
At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.
