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Immunology Update - April 2017

Welcome to the next installment of our regular update where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past few weeks.

Congenital virus evades immune system by destroying surface proteins

​Cytomegalovirus (CMV) is a lifelong condition that causes few symptoms in most people, but can pose a serious risk to unborn babies if a mother is infected with the virus during pregnancy. CMV infected cells are able to hide from the immune system by evading detection from natural killer cells. A study led by Cardiff University has begun to shed some light on how CMV escapes detection and which viral genes are involved.

For this study, published in eLIFE, the researchers infected lab grown cells with deletion mutants of the CMV virus and systematically compared the proteins on the surface of these cells with cells infected with wild-type CMV. The researchers identified a CMV gene family (US12) that allows the infected cells to evade detection by destroying proteins at the surface of the cell, which are produced in response to a viral infection. 

CMV is responsible for 1,000 birth defects a year in the UK and is one of the main causes of child disability and these findings could provide a novel therapeutic target.

BSI Forum member and lead author Dr Ceri Fielding from Cardiff University’s School of Medicine said: “In addition to providing new information that could help develop novel treatments or a cure for this virus, the findings can also tell us more about how our immune system recognizes virus infections beyond CMV.”

Read the press release

Read the full article: Fielding et al. 2017 eLIFE doi: 10.7554/eLife.22206

A novel role for eosinophils in obesity related disorders

Eosinophils are immune cells that play a beneficial role in host defence against parasitic infections and are active participants in many immune responses. However, a new study published in Scientific Reports proposes a novel role for these immune cells in preventing type II diabetes and hypertension.

Eosinophils can be found in the perivascular adipose tissue (PVAT) which surrounds blood vessels, and the anti-contractile effect of this tissue helps maintain normal vascular function. Collaborative work between the University of Manchester, University of Lund and University of Salford showed obese mice to have impaired PVAT function and the number of eosinophils present in the tissue to be significantly reduced.

Lead author and BSI trustee Dr Sheena Cruickshank said: “Our study showed that in fact the secretions from eosinophils have a profound effect on how the blood vessels operate and when they are missing, as in obesity, serious health problems can start to develop.”

Using a mouse-model for eosinophil deficiency, the researchers showed that the addition of eosinophils could restore PVAT function. The potent restorative capability of these immune cells makes them an exciting potential drug target for obesity related disorders such as hypertension and type II diabetes. 

Dr Cruickshank said, “They seem to be incredibly important in a number of processes and this presents us with an exciting new area to investigate for a whole range of illnesses.”

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Read the full article: Withers et al. 2017 Scientific Reports doi: 10.1038/srep44571

Aging causes genetic variability in the immune system

Why do our immune systems weaken with age? A team of researchers from the University of Cambridge, the European bioinformatics institute (EMBL-EBI) and the Wellcome Trust Sanger Institute are trying to answer this exact question using single cell sequencing.

To understand how aging impacts the immune system at the molecular level, the researchers carried out single cell RNA sequencing of stimulated and unstimulated naïve and memory T cells in both young and old mice.  The results from the study, which are published in Science, show that cell-to-cell variability increases with age, and loss of coordination between cells weakens the immune response, making it less effective against infection.

Dr Duncan Odom, at the CRUK-CI says, “Imagine the immune system as a ‘cell army’, ready to protect the body from infection. Our research revealed that this army is well coordinated in young animals, with all the cells working together and operating like a Greek phalanx to block the infection.” Discussing when this coordination breaks down with age he adds, “Although individual cells might still be strong, the lack of coordination between them makes their collective effectiveness lower”.

Aging increased heterogeneity of gene expression in other immune cells, suggesting that loss of coordination between cells could be a common effect of aging in most mammalian tissues.

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Read the full article: Martinez-Jimenez et al. 2017 Science doi: 10.1126/science.aah4115

An alternative therapeutic target for inflammatory bowel disease

Cross section of small intestine​Anti-TNF therapy has been the only treatment for inflammatory bowel disease (IBD) for almost 20 years. However, a research group at University of Oxford have found a potential new therapeutic target which could treat the 40% of patients who do not respond to anti-TNF therapy.

The study, published in Nature Medicine, identified an increase in the amount of the cytokine Oncostatin M (OSM) in the inflamed intestine of IBD patients, suggesting OSM could be an alternative target for treating IBD. The researchers also found that patients with higher OSM levels in their gut were less responsive to anti-TNF therapy and OSM levels could predict how patients would respond to treatment.

“This is a very important finding, because at the moment we are unable to predict which patients will respond well to current therapies; this has an impact on the care we are able to provide to these patients,” said BSI member and lead researcher of the study Professor Fiona Powrie. “With around two million patients worldwide not responding to the current treatment, it is of paramount importance to find new therapies for IBD. The identification of OSM as a new disease mediator in these patients offers hope for new therapies that can be tested in the clinic.”

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Read the full article: West et al. 2017 Nature Medicine doi: 10.1038/nm.4307