Alveolar Macrophages Undergo a Postnatal Transition from a Hyperphagocytic and Proinflammatory Profile to a Tolerogenic Profile

Alveolar Macrophages (AMs) are crucial for lung immunity and homeostasis. While the ontogeny of AMs is well characterized, their postnatal phenotypic and functional maturation remains unclear. Here, we developed a bronchoalveolar lavage (BAL) protocol across key developmental stages and systematically analyzed age-dependent changes in AMs. AM numbers increased with age, acquiring a mature phenotype alongside alveolar maturation.BAL-recovered AMs decreased in size and increased in roundness from day 3 onward and revealed distinct gene expression profiles across different ages. Functionally, phagocytic capacity peaked in 3-day-old mice. Furthermore, AMs from all ages beyond day 1 showed lower basal inflammatory cytokine expression and an attenuated response to LPS, indicating a postnatal transition toward a tolerant phenotype. The transition from a hyper-phagocytic, pro_x0002_inflammatory neonatal profile to a tolerogenic adult phenotype underscores the intrinsic adaptation of AMs to the immunotolerant microenvironment of the mature lung. Our study provides a comprehensive kinetic profile of postnatal AM development.