Key mechanism for controlling body's inflammatory response discovered

September 30, 2012

Researchers at Queen Mary, University of London have discovered how a key molecule controls the body's inflammatory responses. The molecule, known as p110delta, fine-tunes inflammation to avoid excessive reactions that can damage the organism. The findings, published in Nature Immunology today, could be exploited in vaccine development and new cancer therapies.

A healthy immune system reacts to danger signals – from microorganisms such as bacteria and viruses, or from the body's own , such as . This tightly controlled reaction starts with an inflammatory phase that alerts and activates the body to react against the danger signals. Once the danger has been cleared, it is critical that the body's inflammatory phase is shut down to avoid overreaction.

Control over the timing of inflammation is essential and is disrupted in a range of diseases: inflammation that is triggered too quickly or not controlled appropriately can lead to a potentially lethal endotoxic (septic) shock or, in a more chronic state, contribute to the development of diseases such as cancer, arthritis, asthma and multiple sclerosis.

A better understanding of the involved in orchestrating the body's will help in the development of better and more targeted treatments for a variety of diseases.

Professor Bart Vanhaesebroeck, from the Barts Cancer Institute at Queen Mary, University of London, who supervised the research, said: "For years scientists have been puzzled by the way in which p110delta can both fuel and restrain inflammatory reactions in the body. Thanks to the improved understanding that we have achieved through use of genetics and pharmacology, we have now identified one of the specific pathways that p110delta controls."

The researchers found that p110delta balances the immune response by regulating a particular type of immune cell, the dendritic cell. These cells sense and initiate an immune response, primarily provoking inflammation when they encounter "foreign bodies", including bacteria. By using from mice that lacked active p110delta, the study found that p110delta controls the transition of a bacteria-sensing receptor (TLR4) from the surface of the dendritic cell into its interior, a key step which allows the dendritic cell to initiate the shut-down phase of the inflammation.

Dr Ezra Aksoy, from the Barts Cancer Institute, the first author of the paper, said: "Temporarily interfering with p110delta activity could allow us to modulate the balance between the inflammatory and anti-inflammatory pathways, opening up new therapeutic avenues to be exploited in the fields of vaccination, cancer immunotherapy and chronic inflammatory diseases."

Explore further: Dendritic cells control lymphocyte entry into lymph nodes

Related Stories

Dendritic cells control lymphocyte entry into lymph nodes

November 17, 2011
Dendritic cells, discovered in 1973 by Ralph Steinman (2011 Nobel prize in Physiology or Medicine) and known for their role as sentinels of the immune system, have an essential function in the development of high endothelial ...

Gatekeeper signal controls skin inflammation

January 26, 2012
A new study unravels key signals that regulate protective and sometimes pathological inflammation of the skin. The research, published online on January 26th in the journal Immunity by Cell Press, identifies a "gatekeeper" ...

Recommended for you

Gene immunotherapy protects against multiple sclerosis in mice

September 21, 2017
A potent and long-lasting gene immunotherapy approach prevents and reverses symptoms of multiple sclerosis in mice, according to a study published September 21st in the journal Molecular Therapy. Multiple sclerosis is an ...

New academic study reveals true extent of the link between hard water and eczema

September 21, 2017
Hard water damages our protective skin barrier and could contribute to the development of eczema, a new study has shown.

Exposure to pet and pest allergens during infancy linked to reduced asthma risk

September 19, 2017
Children exposed to high indoor levels of pet or pest allergens during infancy have a lower risk of developing asthma by 7 years of age, new research supported by the National Institutes of Health reveals. The findings, published ...

Cholesterol-like molecules switch off the engine in cancer-targeting 'Natural Killer' cells

September 18, 2017
Scientists have just discovered how the engine that powers cancer-killing cells functions. Crucially, their research also highlights how that engine is fuelled and that cholesterol-like molecules, called oxysterols, act as ...

MicroRNA helps cancer evade immune system

September 18, 2017
The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor ...

'Exciting' discovery on path to develop new type of vaccine to treat global viruses

September 15, 2017
Scientists at the University of Southampton have made a significant discovery in efforts to develop a vaccine against Zika, dengue and Hepatitis C viruses that affect millions of people around the world.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.