Efferocytosis

T cells are central to immune system function, and expand dramatically in number in response to threats. Following this expansion and having carried out their role, the cells need to be rapidly cleared, and undergo a type of cell death called apoptosis. Apoptosis is a homeostatic form of cell death designed not to trigger inflammation. However, if apoptotic cells are not rapidly cleared they become necrotic, which is a highly inflammatory type of cell death and can lead to widespread inflammatory conditions. Thus, understanding mechanistically how apoptotic T cells are cleared is important to avoid and treat such inflammation-related diseases. We have established model systems for investigating clearance of dying T cells by scavenging cells called macrophages, and have studied molecular events taking place at the T cell membrane during apoptosis. We have identified a set of molecules called mucins that provide a protective barrier on the surface of the T cell under healthy conditions but which are shed by a membrane protease during apoptotic cell death to allow clearance by macrophages. These findings will help us to understand how we might modulate cell surface molecules during cell death to avoid inflammatory disease outcomes.

Checkout our latest pre-print here:
Drexhage, L. Z., Zhang, S., DuPont, M., Ragaller, F., Sjule, E., Caballero, J. C., Deimel, L., Robertson, H., Russell, R. A., Dushek, O., Sezgin, E., Karaji, N., & Sattentau, Q. J. (2023). Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis. BioRxiv, 2023.08.22.554267. https://doi.org/10.1101/2023.08.22.554267