Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

17.01.2011
Scientists have identified a protein that acts as a 'master switch' in certain white blood cells, determining whether they promote or inhibit inflammation

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.

The study was funded by the Medical Research Council, the European Community, and Arthritis Research UK.

For further information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248
Notes to editors:
1. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Website: www.imperial.ac.uk

2. About the Medical Research Council

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.

Website: www.mrc.ac.uk/

3. About Arthritis Research UK

Arthritis Research UK is the leading authority on arthritis in the UK, conducting scientific and medical research into all types of arthritis and musculoskeletal conditions. It is the UK's fourth largest medical research charity and the only charity solely committed to funding high quality research into the cause, treatment and cure of arthritis.

Website: www.arthritisresearchuk.org

Sam Wong | EurekAlert!
Further information:
http://www.imperial.ac.uk

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>