Apoptosis and cell clearance: Molecular mechanisms and implications for human disease
Apoptosis is a highly regulated process of cell deletion and plays a fundamental role in the maintenance of tissue homeostasis in the adult organism. Many human diseases can be attributed directly or indirectly to a derangement of apoptosis, resulting in either cell accumulation, in which cell eradication or cell turnover is impaired, or cell loss, in which the apoptotic program is inadvertently triggered (Fadeel & Orrenius, J. Intern. Med., 2005; Fadeel, et al., Cell Death Differ., 2008). Moreover, defective macrophage engulfment and degradation of cell corpses may also contribute to a dysregulation of tissue homeostasis (Fadeel & Xue, Crit. Rev. Biochem. Mol. Biol., 2009; Fadeel, Xue, Kagan, Biochem. Biophys. Res. Commun. 2010).
One of our main areas of interest is to understand the molecular regulation of cell death and cell clearance by cells of the immune system and the relevance of these processes in chronic inflammation and autoimmune disease (principal funding: Swedish Research Council: Senior Investigator Award; and Karolinska Institutet: Strategic Professorship). We coined the term programmed cell clearance to describe the process of macrophage recognition and disposal of apoptotic cells in order to emphasize that this is a genetically regulated and evolutionarily conserved process. We are currently aiming to dissect the mechanism of macrophage clearance not only of apoptotic cells but also the disposal of organelles or other subcellular structures that are released from dying cells under various pathological conditions and which could act as danger signals to activate inadvertent immune responses. We are engaged in long-standing collaborations with several other researchers including Prof. Valerian Kagan (University of Pittsburgh) and Prof. Ding Xue (University of Colorado).