If you think the liver’s only relationship with cholesterol is to control its metabolism and excretion, think again. It turns out the liver is also involved in the immune response towards cholesterol particularly in situations where cholesterol is increased, a recent study published in the Circulation Research journal shows.
In a previous post, I wrote about how complex the relationship between heart disease and the immune system is. While most studies that examine the role of the immune system in atherosclerosis focus on immune cells from the blood, lymphoid organs, or look at the immune cells in the aortic walls, there are very few studies that looked at the contribution of the immune system in the liver to atherosclerosis development.
As an immunological site, the liver plays an important role in preventing autoimmunity and defending against invaders. Being the largest solid organ in the body, with its rich blood flow and its proximity to the digestive system, the liver is a crucial organ in cholesterol metabolism. The liver is also filled with macrophages, an immune cell that, among its many jobs, specializes in getting rid of extra cholesterol. High cholesterol levels can destroy the liver’s ability to metabolize cholesterol and result in liver failure. However, not much is known about the role of the immune cells in the liver and how do they respond to high cholesterol levels. A research group from the Cardiovascular Medicine Unit in Karolinska Institute, Sweden, examined this exact question. Their study shows that in mouse models, T cells, a type of immune cell that is involved in adaptive immunity, increases in the liver as a result of high cholesterol levels. These liver T cells can travel to the aortic vessels were atherosclerosis occurs, providing first evidence that the liver immune cells may contribute to the immune response during atherosclerosis development.
As an immunologist who studies how the immune system affects atherosclerosis development, I am constantly fascinated by new findings in this area. The study made me think of whether the liver’s immune response is responding to the excess cholesterol in the circulation or to that accumulating in the liver. As there are different types of T cells, some that promote atherosclerosis while others reduce disease progression, the study also made me wonder if these different cells generated in the liver tipped the balance in favor or against a protective immune response. Does a similar immune response happen in the liver of people with high cholesterol levels? With these new findings, the door is now open to questions that will help our understanding of the complex relationship between cholesterol, the liver, the immune system and how it all ties together to influence atherosclerosis and heart disease.
Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.