Efferocytosis in multisystem diseases

Efferocytosis, the phagocytosis of apoptotic cells performed by both specialized phagocytes (such as macrophages) and non-specialized phagocytes (such as epithelial cells), is involved in tissue repair and homeostasis. Effective efferocytosis prevents secondary necrosis, terminates inflammatory responses, promotes self-tolerance and activates pro-resolving pathways to maintain homeostasis. When efferocytosis is impaired, apoptotic cells that could not be cleared in time aggregate, resulting in the necrosis of apoptotic cells and release of pro-inflammatory factors. In addition, defective efferocytosis inhibits the intracellular cholesterol reverse transportation pathways, which may lead to atherosclerosis, lung damage, non-alcoholic fatty liver disease and neurodegenerative diseases. The uncleared apoptotic cells can also release autoantigens, which can cause autoimmune diseases. Cancer cells escape from phagocytosis via efferocytosis. Therefore, new treatment strategies for diseases related to defective efferocytosis are proposed. This review illustrated the mechanisms of efferocytosis in multisystem diseases and organismal homeostasis and the pathophysiological consequences of defective efferocytosis. Several drugs and treatments available to enhance efferocytosis are also mentioned in the review, serving as new evidence for clinical application.