Macrophages play essential roles in tissue homeostasis, defense, and repair. Their functions are highly tissue-specific, and when
damage and inflammation stimulate repopulation by circulating monocytes, the incoming monocytes rapidly acquire the same,
tissue-specific functions as the previous, resident macrophages. Several environmental factors are thought to guide the functional
differentiation of recruited monocytes, including metabolic pressures imposed by the fuel sources available in each tissue. Here we
discuss whether such a model of metabolic determinism can be applied to macrophage differentiation across barrier sites, from the
lung to the skin. We suggest an alternative model, in which metabolic phenotype is a consequence of macrophage longevity rather
than an early driver of tissue-specific adaption
