Understanding the alveolar macrophage niche in health and disease

01 January 2023 → 31 December 2026
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Allergology
    • Inflammation
    • Innate immunity
    • Respiratory medicine
Macrophage niche signals Trained Immunity
Project description

Alveolar macrophages (AMs) are the most abundant immune cell type present in the healthy lung, acting as vacuum cleaners that maintain lung homeostasis. They fulfill a generic function as sentinel phagocytic immune cell, but also have a unique metabolic and repair function, essential for homeostasis of the alveolar compartment and prevention of lung disease. Like other tissue resident macrophages, AMs live in a specific niche, that provides the nurturing signals for AMs to thrive. We hypothesize that niche signals derived from alveolar epithelial cells, capillary endothelial cells and alveolar interstitial fibroblasts are crucial for inducing proper AM development and programming. Using a newly developed mouse model allowing for inducible depletion of AMs, followed by niche filling by newcomer progenitors, we will study the molecular and epigenetic control, the nature of the signals that regulate AM development and programming by scRNAseq and CUT&Run epigenetics. We will validate these findings using a CRISPR/Cas9 tool where we selectively impose genetic perturbations in precursors cells and track their development in AMdepleted mice. Finally, we will assess whether chronic environmental exposure to cigarette smoke or farm dust alters the alveolar niche communication, AM heterogeneity and AM epigenetic landscape to alter trained innate immunity and adaptive immunity.