To summarize macrophage functional states in homeostasis and across various lung diseases, emphasizing their plasticity and the impact of the microenvironment.
Approach:
Key Findings:
Macrophage functions are not adequately captured by the M1/M2 dichotomy.
Macrophage transcriptional programs are influenced by ontogeny, tissue niche, and epigenetic–metabolic regulation.
Persistent tissue injury and microenvironmental stress lead to remodeling of resident macrophage programs and differentiation of recruited monocyte-derived macrophages.
Macrophage states are linked to inflammatory amplification, epithelial and endothelial barrier dysfunction, extracellular matrix remodeling, and tumor immune evasion.
Candidate communication axes between macrophages and other cell types have been identified, some of which appear partially conserved across disease contexts.
Interpretation:
The study highlights the complexity of macrophage behavior in lung diseases.
Limitations:
The study does not provide a comprehensive overview of all macrophage functions in every lung disease.
Species differences and varying levels of experimental support may affect the generalizability of findings.
Conclusion:
Decoding the spatiotemporal dynamics and communication networks of macrophages may clarify mechanisms of tissue remodeling and macrophage-targeted intervention in pulmonary diseases.
