Abstract
At birth, the lungs experience a sudden transition from a pathogen-free, hypoxic, fluid-filled environment to a pathogen-rich, rhythmically distended air-liquid interface. While many studies focus on adult tissue, the heterogeneity of immune cells in the perinatal lung remains unexplored. Here, we combine single cell transcriptomics with in situ hybridization to present an atlas of the murine lung immune compartment from E18.5 to P21, a critical period of lung 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 complex and dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed five distinct subpopulations, with both unique gene expression signatures and developmental gradients and localizing specifically to the lung parenchyma, vessels and airways, suggesting distinct physiological functions in tissue remodeling, angiogenesis, and immunity. Three dendritic cell populations, basophils, mast cells and neutrophils appear poised for rapid immune response. In contrast, although lymphocytes increased in abundance during early postnatal life, they remained functionally immature. These data identify a marked increase in lung cell immune diversity concomitant with the transition from fetal to air-breathing life, with precise orchestration of unique macrophage subpopulations across postnatal development to fill context-specific structural and immunomodulatory functions. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter lung immune cell phenotype during a period of rapid growth and heightened vulnerability.
