Metabolic regulation of innate immune cell phenotypes during wound repair and regeneration

Metabolism regulates an array of cellular processes from embryonic development through adulthood. These include proliferation, differentiation and the effector functions of adult cells to maintain homeostasis and repair. It is becoming clear that bioenergetic shifts can control how cells respond to environmental disruptions during tissue injury to initiate a healing response. Specifically, innate immune cells shift their phenotypes to initiate and resolve inflammation, and there is intense interest to understand how these responses might regulate healing outcomes. Here, we review recent literature describing how cellular metabolism and metabolic byproducts regulate phenotype conversions among innate immune cells. Although most studies of this kind do not focus on tissue damage, we discuss how metabolic regulation of these phenotypes promotes tissue repair. In particular, we provide a framework for considering the extent to which altering the innate immune response might shift fibrotic repair towards regenerative healing.