Researchers from Stanford University and Stanford School of Medicine have discovered a dramatic increase in the types and number of immune cells in the lungs of mice just before birth through the first weeks of life.

Their study, “Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution,” was published in eLife and led by Racquel Domingo-Gonzalez, PhD, who was a postdoctoral scholar at the department of pediatrics, Stanford University School of Medicine, when the study was carried out.

A baby’s first breath is a profound change at birth as its lungs, which were filled with fluid during pregnancy, must suddenly fill with oxygen from the air. At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Many studies have focused on the adult lung, yet the perinatal lung remains unexplored. “How these changes affect immune cell populations during this transition and the ensuing rapid lung growth after birth is unclear,” noted Domingo-Gonzalez.

To learn more, Domingo-Gonzalez and her team used a technique called single-cell transcriptomics to track gene expression in individual immune cells in the lungs of mice just before birth and through the first three weeks of life.

“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,” the researchers wrote.

The team discovered that just before birth, macrophages—immune cells involved in the detection, phagocytosis, and destruction of bacteria and other harmful organisms—encircle the small blood vessels in the lungs, likely stimulating them to grow. After birth, a large number of many different types of immune cells appear, including those needed for blood-vessel growth, lung development, and to fight off infections.

These findings may offer insight into why disruptions to the immune system early in life caused by infections, excessive levels of oxygen, or steroid drugs may lead to life-long lung problems.

“Injuries to the immature lung can have profound, life-long consequences since a significant component of lung development occurs during late pregnancy and the first few years of postnatal life,” stated co-lead author Fabio Zanini, who was a postdoctoral fellow in Stephen Quake’s lab at Stanford University when the study was initiated.

These discoveries can help scientists understand why early development can lead to breathing problems such as asthma later in life, and may eventually lead to therapies to preserve or enhance lung development in infants and young children.

“Our work lays the foundation for further studies on the diversity of immune cells and their roles during this important window of lung development,” noted senior author Cristina Alvira, MD, associate professor of pediatrics at Stanford University School of Medicine.

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