Apoptotic cell clearance: basic biology and therapeutic potential

The removal of apoptotic cells by phagocytes is essential for the maintenance of tissue homeostasis and is usually immunologically silent. However, dysregulation of this process is associated with numerous inflammatory and autoimmune diseases, and thus the therapeutic manipulation of apoptotic cell clearance by phagocytes may be a means to treat these diseases. The prompt removal of apoptotic cells by phagocytes is important for maintaining tissue homeostasis. The molecular and cellular events that underpin apoptotic cell recognition and uptake, and the subsequent biological responses, are increasingly better defined. The detection and disposal of apoptotic cells generally promote an anti-inflammatory response at the tissue level, as well as immunological tolerance. Consequently, defects in apoptotic cell clearance have been linked with various inflammatory diseases and autoimmunity. Conversely, under certain conditions, such as the killing of tumour cells by specific cell-death inducers, the recognition of apoptotic tumour cells can promote an immunogenic response and antitumour immunity. Here, we review the current understanding of the complex process of apoptotic cell clearance in physiology and pathology, and discuss how this knowledge could be harnessed for new therapeutic strategies.