Scientists have discovered a new metabolic process in the body that can switch off inflammation. They have discovered that ‘itaconate’ – a molecule derived from glucose – acts as a powerful off-switch for macrophages, which are the cells in the immune system that lie at the heart of many inflammatory diseases including arthritis, inflammatory bowel disease and heart disease.
The scientists, working in the School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute at Trinity College Dublin, hope their discovery will have relevance for inflammatory and infectious diseases – and that their findings may also help to develop much-needed new drugs to treat people living with these conditions.
Professor of Biochemistry at Trinity, Luke O’Neill, was, along with Dr Mike Murphy of the University of Cambridge, the joint leader of the work just published in leading international journal Nature. The discoveries were made using both human cells and mice as a model organism.
Professor O’Neill said: “My lab has been exploring metabolic changes in macrophages for the past six years and we’ve come across what we think is the most important finding yet.”
“It is well known that macrophages cause inflammation, but we have just found that they can be coaxed to make a biochemical called itaconate. This functions as an important brake, or off-switch, on the macrophage, cooling the heat of inflammation in a process never before described.”
Dr Evanna Mills, who, with Dylan Ryan was joint first author of the work, said: “The macrophage takes the nutrient glucose, whose day job it is to provide energy, and surprisingly turns it into itaconate. This then blocks production of inflammatory factors, and also protects mice from the lethal inflammation that can occur during infection.”
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