PROGRAMMED Cell Clearance: Molecular Mechanisms and Role in Autoimmune Disease, Chronic Inflammation, and Anti-Cancer Immune Responses

During normal development and tissue turnover, cells are programmed to undergo apoptosis and cell corpses are subsequently removed by professional phagocytes (macrophages) or other neighboring cells. The recognition and engulfment of apoptotic cell corpses, a complex and dynamic process which we have termed programmed cell clearance, is thought to prevent chronic inflammation through the disposal of dying cells prior to the leakage from these cells of noxious constituents into surrounding tissues. Moreover, rapid engulfment of apoptotic cells, orchestrated through the interaction of numerous recognition or “eat-me” signals, bridging molecules, and engulfment receptors, is believed to prevent inadvertent immune responses to self antigen present within or on the surface of dying cells. Finally, while engulfment of apoptotic cells is generally considered to be a silent process from an immunological perspective, recognition and uptake of apoptotic cell corpses by antigen-presenting dendritic cells may in some cases trigger an immunogenic response, suggesting that the process of programmed cell clearance could be harnessed for therapeutic purposes to improve cancer treatment. The present review will discuss the molecular mechanisms of programmed cell clearance, as well as the role of this fundamental process in inflammation, autoimmune disease, and anti-cancer immune responses.