How does binding of antibodies to macrophages cause inflammation in autoimmune diseases?
Lead applicant - Dr Menna Clatworthy
Organisation - University of Cambridge
Type of grant - Invited Research Award
Status of grant - Active
Amount of the original award - £351,727
Start date - 1 March 2018
Reference - 21777
What are the aims of this research?
Antibodies are molecules that normally help to fight infections by binding to invading foreign substances, such as bacteria and viruses, and to cells of the immune system, causing these immune cells to become activated. Antibodies can cause inflammation in some autoimmune diseases, such as lupus and rheumatoid arthritis, where they bind to the body's own tissues.
This research aims to address why it is that binding of an antibody to a particular cell in the body's immune system, the macrophage, is able to cause changes to the way that the macrophage generates energy, resulting in it producing more toxins and inflammatory signals.
Why is this research important?
The researchers have previously found that when antibodies bind to one particular immune cell, the macrophage, this causes a switch in the way these cells generate energy, in a process called metabolism. This switch in metabolism can make the macrophages produce inflammation and toxic molecules. The researchers now aim to identify whether they can reduce inflammation and tissue damage if they block this switch. This might help to identify a new pathway that could be targeted by drugs.
In this research, macrophages will be taken from human blood and cultured in a dish. Antibodies will be made to bind to these macrophages, therefore causing changes to their metabolism. Drugs will then be used to see whether this change in metabolism can be blocked (meaning that the cultured macrophages produce less inflammatory signals and toxic molecules). To test whether this could work as a treatment strategy in a disease, not just a dish, the researchers will also block the same pathway in mice with arthritis and kidney inflammation that is caused by antibodies.
How will the findings benefit patients?
Antibodies can cause inflammation and damage in many tissues, for example, joints, kidneys, skin and lungs, in a number of rheumatic diseases. An understanding of the processes that result in this inflammation could help to identify new treatment strategies that make the disease better and improve quality of life for many patients.