Navigation Links
Scientists find the 'master switch' for key immune cells in inflammatory diseases

Scientists have identified a protein that acts as a "master switch" in certain white blood cells, determining whether they promote or inhibit inflammation. The study, published in the journal Nature Immunology, could help researchers look for new treatments for diseases such as rheumatoid arthritis that involve excessive inflammation.

Inflammatory responses are an important defence that the body uses against harmful stimuli such as infections or tissue damage, but in many conditions, excessive inflammation can itself harm the body. In rheumatoid arthritis, the joints become swollen and painful, but the reasons why this happens are not well understood.

Cells of the immune system called macrophages can either stimulate inflammation or suppress it by releasing chemical signals that alter the behaviour of other cells. The new study, by scientists from Imperial College London, has shown that a protein called IRF5 acts as a molecular switch that controls whether macrophages promote or inhibit inflammation.

The results 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.

Researchers from Imperial College London previously developed anti-TNF treatments, a class of drug that is widely used as a treatment for rheumatoid arthritis. The drugs target TNF, an important signalling chemical released by immune cells to stimulate inflammatory responses. However, about 30 per cent of patients don't respond to anti-TNF drugs, so there is a serious need to develop more widely effective therapies.

Dr Irina Udalova from the Kennedy Institute of Rheumatology at Imperial College London, the senior researcher on the study, said:

"Diseases can affect which genes are switched on and off in particular types of cells. Understanding how this switching is regulated is crucial for designing targeted strategies to suppress unwanted cell responses.

"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

Related biology news :

1. Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells
2. Scientists identify novel inhibitor of human microRNA
3. Argonne scientists peer into heart of compound that may detect chemical, biological weapons
4. MU scientists go green with gold, distribute environmentally friendly nanoparticles
5. Scientists identify gene that may contribute to improved rice yield
6. Scientists discover why a mothers high-fat diet contributes to obesity in her children
7. MU scientists see how HIV matures into an infection
8. Earth scientists keep an eye on Texas
9. Thinking it through: Scientists call for policy to guide biofuels industry toward sustainability
10. Scientists identify a molecule that coordinates the movement of cells
11. Scientists Find new migratory patterns for Mediterranean and Western Atlantic bluefin tuna
Post Your Comments:
(Date:11/17/2015)... 17, 2015 Pressure BioSciences, Inc. (OTCQB: PBIO) ... and sale of broadly enabling, pressure cycling technology ("PCT")-based ... today announced it has received gross proceeds of $745,000 ... Placement (the "Offering"), increasing the total amount raised to ... additional closings are expected in the near future. ...
(Date:11/11/2015)...   MedNet Solutions , an innovative SaaS-based eClinical technology ... pleased to announce that it will be a Sponsor of ... to be held November 17-19 in Hamburg ... of iMedNet , MedNet,s easy-to-use, proven and ... has been able to deliver time and cost savings of ...
(Date:11/4/2015)... , November 4, 2015 ... market report published by Transparency Market Research "Home Security Solutions ... and Forecast 2015 - 2022", the global home security solutions ... bn by 2022. The market is estimated to expand ... from 2015 to 2022. Rising security needs among customers ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , November 25, 2015 Studies ... and human plaque and pave the way for more effective ... in cats     --> ... commonly diagnosed health problems in cats, yet relatively little was ... Two collaborative studies have been conducted by researchers from the ...
(Date:11/25/2015)... ... November 25, 2015 , ... A long-standing partnership ... Professionals (OPBAP) has been formalized with the signing of a Memorandum of Understanding. ... OPBAP leaders Capt. Karl Minter and Capt. Albert Glenn Tuesday, November 24, 2015, ...
(Date:11/24/2015)... Malaysia , Nov. 24, 2015  Asia-Pacific ... contract research organisation (CRO) market. The trend of ... in lower margins but higher volume share for ... capacity and scale, however, margins in the CRO ... Organisation (CRO) Market ( ), finds ...
(Date:11/24/2015)... , Nov. 24, 2015 /CNW/ - iCo Therapeutics ("iCo" ... reported financial results for the quarter ended September ... in Canadian dollars and presented under International Financial ... States ," said Andrew Rae , ... regarding iCo-008 are not only value enriching for ...
Breaking Biology Technology: