"Our results show that IRF5 is the master switch in a key set of immune cells, which determines the profile of genes that get turned on in those cells. This is really exciting because it means that if we can design molecules that interfere with IRF5 function, it could give us new anti-inflammatory treatments for a wide variety of conditions."
Gene association studies have linked variations in the gene that encodes IRF5 with an increased risk of autoimmune diseases. This led Dr Udalova and a PhD student in her lab, Mr Thomas Krausgruber, to investigate what role the protein plays in controlling inflammation.
They used engineered viruses to introduce extra copies of the IRF5 gene in human macrophages grown in the laboratory, making the cells produce more IRF5. When they did this to macrophages with anti-inflammatory characteristics, it made them switch to promoting inflammation. When they blocked IRF5 in pro-inflammatory macrophages using synthetic molecules, this reduced the cells' production of signals that promote inflammation. The researchers also studied genetically modified mice that were unable to produce IRF5. These mice produced lower levels of chemical signals that stimulate inflammation.
IRF5 seems to work by switching on genes that stimulate inflammatory responses and dampening genes that inhibit them. It can either do this by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on. Dr Udalova's group are now studying how IRF5 works at a molecular level and which other proteins it interacts with so that they can design ways to block its effects.
|Contact: Sam Wong|
Imperial College London