Roles of efferocytosis in wound repair: Process, cells, and signals

Efficient clearance of apoptotic cells, termed efferocytosis, is essential for resolving excessive inflammation, promoting wound repair, and maintaining homeostasis. Defective clearance results in the accumulation of dead cells and other metabolites, which are responsible for chronic inflammation, nonhealing of wounds, and tissue regeneration. Emerging evidence shows that the failure to resolve inflammation and defective phagocytosis or efferocytosis increases the possibility of several diseases involving diabetic wounds and damage to the gastrointestinal mucosa in patients with inflammatory bowel disease, which is a focus of medical development and the public eye. Thus, gaining deeper insight into the molecular and cellular mechanisms of efferocytosis may be useful for inflammation resolution. This review describes the mechanism of efferocytosis and wound repair and the roles of professionals (macrophages and dendritic cells) and amateur phagocytes (e.g., epithelial cells, endothelial cells, and fibroblasts) in both processes, which may provide insight into how efferocytosis affects wound repair. Because there may be many inflammatory cells recruited to the injury area, the aim of efferocytosis is to clear these cells and release proinflammatory and anti-inflammatory mediators to promote repair. Here, we review the effects of cell-mediated efferocytosis on the timely efferocytosis of neutrophils and M1 macrophages and the relationship between M2 polarization and efferocytosis. In addition, the molecular mechanisms involved are discussed, which may further our understanding of the effects of efferocytosis. Finally, these signals also provide potential targets for tissue repair intervention.