Hijacking immune checkpoints to prevent the build-up of fatty plaques

The immune checkpoint CD200-CD200R as a therapeutic pathway in cardiovascular disease

White blood cells involved in inflammation play a key role in the development of fatty plaques that form in our arteries (atherosclerosis). Some white blood cells, called macrophages and monocytes, are controlled by many checkpoints to regulate this inflammation. A checkpoint called CD200 is known to control of those cells by interacting with its partner molecule, CD200R. Professor Monaco and team have shown that loss of CD200 molecules increases the influx of monocytes and promotes fatty plaque build-up. In this project they aim to learn exactly how CD200R controls the supply of these cells, and how they are switched on. They will delete the CD200R gene from mice that are prone to atherosclerosis and compare the numbers of different types of white blood cells with mice that still have the CD200R checkpoint in place. They will also use state-of-the-art technology called mass cytometry to distinguish between white blood cells that were already at the site of atherosclerosis and those that have been recruited. By understanding more about how this checkpoint works, they hope to identify and develop treatments that prevent atherosclerosis by regulating the release and activation of white blood cells.