Phagocytic Clearance of Dying Cells:
Mechanisms and Consequences
Engulfment of apoptotic germ cells (CypHer) by murine Sertoli cells in vitro (phalloidin and DAPI). more info...
Apoptosis is a crucial physiologic process that occurs from early mammalian development throughout life in all tissues. Cells programmed to die must be eliminated swiftly to prevent leakage of potentially toxic and immunogenic contents of the dead cells into the surrounding tissue. The primary means for this removal is phagocytosis- a complex and highly efficient process regulated by specific signaling pathways in both the phagocyte and the apoptotic cell. Beyond simply removing dead cell material, phagocytes engulfing apoptotic cells actively influence the immune response by suppressing inflammation and promoting self-tolerance. The failure to efficiently clear apoptotic cells can result in deleterious immunological consequences such as chronic inflammation and autoimmunity and is linked to a wide range of disease states including cancer, atherosclerosis and respiratory illnesses. Thus, apoptotic cell clearance is a fundamental new area of immunology with broad implications for human health and disease.
The goal of our lab is to understand the signaling pathways that regulate how phagocytes locate and engulf apoptotic cells and how this process impacts the immune system in normal and disease states.
- Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 477, 220-4. (2011 Sep 08).
- Phagocytic activity of neuronal progenitors regulates adult neurogenesis. Nat Cell Biol. 13, 1076-83. (2011 Sep 01).
- Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 467, 863-7. (2010 Oct 14).