Efferocytosis research

Efferocytosis is the process of removing and recycling dead and dying cells by phagocytes. Efferocytosis serves multiple functions in the host including promoting normal tissue development, maintaining tissue homeostasis, and controlling pathogen infections. Efferocytosis is carried out mainly by macrophages, which are equipped to rapidly detect, capture, engulf, degrade and recycle dead and dying cells. Efferocytosis of apoptotic cells leads to the induction of an anti-inflammatory macrophage phenotype, whereas cells undergoing inflammatory forms of cell death such as pyroptosis leads to an inflammatory macrophage phenotype. The recognition of dying cells by macrophages is regulated by a balance of so-called 'eat-me' and don't eat-me' signals. We have identified a new family of don't eat-me molecules termed transmembrane mucins that are enzymatically removed during apoptosis and pyroptosis, driving efficient efferocytosis. Since cancer cells frequently express high levels of cell surface mucins to avoid immune surveillance and elimination, approaches to remove these by modulation of cell surface enzyme activity may have implications in cancer therapy.