Researchers find molecular switch that directs proinflammatory response
London – Researchers from Imperial College in London have identified a protein that acts as a master switch in macrophages, determining whether they promote or inhibit inflammation. Overexpression of the transcriptional regulator IRF5 induced transcription of proinflammatory signal molecules in macrophages such as interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19, according to the team headed by Dr Irina Udalova, and blocked immunosilencers such as IL-10 leading to Th1- and TH17 responses (Nature Immunology). In genetically modified mice unable to produce IRF5, they observed significantly lower levels of interleukin signals that stimulate inflammation. The findings suggest that blocking the production of IRF5 in macrophages might be an effective way of treating a wide range of autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, lupus, and multiple sclerosis. In addition, boosting IRF5 levels might help to treat people whose immune systems are compromised. Dr Udalova's group is 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. There is a high medical need for new anti-inflammatory treatment as 30% of arthritis patients are non-responsive to anti-TNF-immunosupressive therapy.