Exploring Steady-State Alveolar Macrophage Cross-Talk and Prenatal Development in the Lungs

The lungs, which are responsible for gas exchange, are constantly threatened by exposure to pathogens in the air. Lung function thus relies on a thin, hardy layer of epithelial cells that line the respiratory tract, and the alveolar macrophages (AMs), which reside within the lumen of the alveoli. AMs engulf pathogens that arrive in the alveolar lumen and maintain steady-state alveolar function. In return, AMs rely on the alveolar niche cells for one critical cytokine: granulocyte-macrophage colony-stimulating factor (GM-CSF). It is not known, however, which cells produce the GM-CSF that supports AM development, and which progenitor cell populations contribute to the adult AM pool. We established that AMs critically rely on alveolar epithelial type 2 cells (AT2s) for GM-CSF not only during adulthood, but also during prenatal development. Additionally, we investigated AM origin using novel genetic tools that could clearly distinguish different myeloid populations in the developing prenatal lung. Overall, these results provide starting points for studies delving further into not only AM cross-talk in the alveolar niche, but also lung macrophage origin and function. $\textit{Full-text embargoed until: 2026-11-11}$