A new paper with one of our School of Translational and Experimental Medicine MRes-PhD students as the lead author, has described a previously unknown role for cholesterol metabolism in cells of the immune system.

The paper, published in Nature communications, describes how cholesterol metabolism acts as a switch for controlling the human immune response. Not only could this help us understand the impact of this metabolism in the immune response, but it could also enable us to understand the effect that drugs such as statins, which target cholesterol, can have on the body’s immune response.

Controlling the immune response is fundamental to keep the body in a healthy state. A healthy immune response activates immune cells to eliminate the danger posed by disease or infection, and once its work is done it also reins the immune cells back to wait for the next challenge.

The team’s research aimed to better understand how the brakes of the immune system work, in order to better identify the differences between healthy immune systems, and to find ways to exploit those brakes when treating human disease. Increasing pressure on the molecular brakes could help individuals with an over reactive immune system, like rheumatoid arthritis, diabetes, psoriasis and other autoimmune disorders.

The team were looking specifically at a chemical called Interleukin 10 (IL-10), one of the most important brakes of the immune system. This is a cytokine, a type of protein important in cell signalling. Last year, our team reported that IL-10 expression is linked to cholesterol metabolism in human T lymphocytes – cells that orchestrate the immune response. The team also found that the cholesterol system in tissues is linked to the risk of developing rheumatoid arthritis.

The team have now discovered that cholesterol metabolism is also important in controlling the expression of IL-10 in human B lymphocytes, the immune cells responsible for producing antibodies. They fully characterised the different proteins involved in the signalling pathway required for B cells to express IL-10. The team also showed that patients with genetic alterations in cholesterol metabolism show defective IL-10 production.

This finding suggests a new potential route for treating autoimmune conditions, such as rheumatoid arthritis.

Professor Rebecca Oakey, STEM academic training lead, said: “The School of Translational and Experimental Medicine team are delighted to highlight a new and exciting publication from one of our non-clinical MRes-PhD trainees as he wraps up his thesis work with a fantastic first author Nature Communications paper. Well done Jack.”

Speaking of this discovery Jack Bibby, who was the lead author on the research, said: “This discovery will help us to better understand the impact of drugs that target cholesterol on the body’s immune system. I am very grateful to the School of Translational and Experimental Medicine at the NIHR Guy’s and St Thomas’ Biomedical Research Centre for funding my MRes-PhD prgramme, which allowed me to play my part in this important work”

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