Master switch for inflammation

A master switch in certain white blood cells determines whether they promote or inhibit inflammation say scientists who believe the finding may lead to new treatments for inflammatory disease

Microphages controlled by a master switch that promotes or inhibits inflammation

Scientists from Imperial College London discovered the protein IRF5 acts as a molecular switch that controls whether macrophages promote or inhibit inflammation. Blocking its production may be an effective way of treating diseases such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Boosting IRF5 levels may also help treat people with compromised immune systems.

“Our results show that the IRF5 is the master switch in a key set of immune cells, which determines the profile of the genes that get turned on in those cells,” said Dr Irinia Udalova from the Kennedy Institute of Rheumatology.

“This is really exciting because it means if we can design molecules that interfere with IRF5 function, it could give us new anti-inflammatory treatments for a wide variety of conditions.”

Udalova and PhD student Thomas Krausgruber engineered viruses to introduce extra copies of the IRF5 gene in human microphages grown in the laboratory, making the cells produce more IRF5. Microphages with anti-inflammatory characteristics switched to promoting inflammation. When IRF5 was blocked in pro-inflammatory macrophages using synthetic molecules, the cells’ signals to promote inflammation were reduced.

The scientists believe IRF5 works by switching on genes that stimulate inflammatory responses and dampening genes that inhibit them, either interacting with DNA directly or with other proteins that control which genes are switched on. Udalova is now studying how the protein works at a molecular level and which other proteins it interacts with to design ways to block its effects.