Professor Federica Marelli-Berg and her team at Queen Mary University of London are fighting transplant rejection by studying the role that inflammation plays in cardiovascular disease.
The immune system and heart disease
Professor Marelli-Berg’s research programme focuses on a type of white blood cell, called a T-cell.
T-cells are essential for the immune response as they protect the body from infections. However, they also cause inflammation which can make a number of cardiovascular diseases worse. For example, they can contribute to the build-up of fatty plaques in blood vessels in atherosclerosis, and are involved in an inflammatory condition of the heart called myocarditis, which can lead to heart failure.
Even cardiovascular metabolic diseases, such as obesity and its complications, are known to be associated with exaggerated T-cell inflammation. T-cells are also a major part of the immune response that results in the rejection of a transplanted heart.
Heart transplant rejection
Around 200 heart transplants take place in the UK each year. Due to advances in medicine, it is now rare for a transplanted heart to be rejected immediately after a transplant occurs. However, it's estimated that around 40% of hearts are rejected within 10 years, resulting in the patients re-joining the ever-growing waiting list for a heart transplant.
Rejection of a transplanted organ occurs when the body’s immune system recognises the new organ as a foreign object and attacks it, just as it would attack an infection.
The role of T-cells
T-cells are responsible for deciding the intensity of this attack against the transplanted organ. During this process the T-cells move from the blood and infiltrate the organ tissue. Professor Marelli-Berg and her team aim to find a way to stop the T-cells from infiltrating heart tissue and hope to be able to prevent transplanted hearts from being rejected.
Homing in on the heart
To find their way to their target, T-cells are armed with a number of surface proteins, or receptors - biological GPS systems that allow them to preferentially travel to some tissues, but not others.
Prof Marelli-Berg’s team has been studying what controls the migration of T-cells to the heart and to sites of inflammation in blood vessels. Recently, her group has identified a new molecular pathway that directs T-cell migration to the heart. They have shown that by blocking this pathway they can prevent rejection of heart transplants without affecting the rest of the immune system.
This breakthrough discovery paves the way for blocking the immune response in the heart selectively without the severe side effects (such as infections and cancer) that affect transplant patients taking conventional immunosuppression, which impairs the whole body’s immune responses.
Blocking the new ‘heart homing’ pathway may also help to combat T-cell infiltration and heart damage in myocarditis – a strategy that Prof Marelli-Berg will explore in her research programme.
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