Immune cells keep cholesterol down

Recent research at Karolinska Institutet describes how liver uptake of cholesterol from the blood is regulated by the immune system. These findings, which are published in The Journal of Clinical Investigation, can explain how a certain type of immune cell prevents atherosclerosis.

It is well known that the build-up of cholesterol in the artery walls elicits atherosclerosis. When immune cells enter the artery wall at the site of this cholesterol accumulation, inflammation ensues and an atherosclerotic plaque develops. This process can lead to myocardial infarction and stroke.

A type of immune cell involved in inhibiting or regulating inflammation is the so-called regulatory T cell. Earlier studies have indirectly suggested that these cells are involved in atherosclerosis, but exactly how they operate remains unclear. The current research at Karolinska Institutet shows that regulatory T cells inhibit atherosclerosis by increasing the uptake of blood cholesterol by the liver.

"We were surprised to find that the regulatory T cells not only reduced the inflammatory process, but also altered the levels of cholesterol in the blood," says team member Professor Göran Hansson of the Centre for Molecular Medicine.

To study the influence of regulatory T cells on the atherosclerotic process, the researchers used a strain of mice with an inherited susceptibility to atherosclerosis. When the regulatory T cells from these mice were removed, cholesterol levels in their blood increased dramatically. The investigators could show that a receptor important in the uptake of cholesterol-rich LDL particles, sortilin-1 was also decreased and caused the effect on blood cholesterol.

"Our results indicate a novel principle for the regulation of cholesterol metabolism," says Professor Göran Hansson. "We hope that our findings will inspire future treatments."

The researchers now hope to ascertain the precise mechanism in which the regulatory T cells are able to control the sortilin receptor levels in the liver. This knowledge will then lead to a better understanding of how blood cholesterol levels can be regulated.