Mucosal Immunol. 2026 Mar 21:S1933-0219(26)00034-6. doi: 10.1016/j.mucimm.2026.03.010. Online ahead of print.
ABSTRACT
Macrophages play important roles in lung homeostasis and disease by interacting with their surrounding tissue microenvironment. Accordingly, macrophage metabolism and local metabolites shape immune responses in the lung. Here, I review the metabolic regulation of lung macrophages and regulation of lung immunity by macrophage metabolism in the context of lung injury, host defense, and tissue repair. First, the intrinsic regulation of macrophages by intracellular metabolism is discussed with a focus on how macrophages adapt to the metabolic milieu of the lung in steady state and when lung homeostasis is disturbed. Second, the extrinsic regulation of macrophages and lung immunity by extracellular metabolites is reviewed. Specifically, I present how metabolites acting on lung macrophages control their function. In addition, I discuss how metabolites produced by macrophages impact lung function. Finally, I provide an overview of future areas of research related to the regulation of lung macrophages by tissue-derived metabolites.
PMID:41871742 | DOI:10.1016/j.mucimm.2026.03.010