Context-dependent regulation of iron metabolism in macrophages

Iron is an essential element that supports a wide range of biological processes.Cellular iron is mainly imported in the ferric (Fe 3+ ) form via transferrin receptor protein 1 (TFR1) and reduced to ferrous (Fe 2+ ) ion which is utilized as the labile iron pool or stored in ferritin.Through multiple regulatory mechanisms, cells control labile iron levels to sustain fundamental processes such as DNA synthesis and mitochondrial respiration and to prevent iron-induced oxidative stress.Given the fundamental role of iron in cellular physiology, recent studies have increasingly focused on how iron regulates immune cell function and development.In particular, macrophages have been extensively studied due to their pivotal role in iron handling, storage, and recycling.Although numerous studies suggest that elevated intracellular iron promotes macrophage polarization toward pro-inflammatory phenotypes, emerging evidence indicates that the consequences of iron regulation in macrophages are more complex and highly disease-dependent.In this review, we summarize current knowledge on the interplay between iron metabolism and macrophage biology and highlight recent findings that reveal context-specific mechanisms across diverse physiology and pathological environment.