Entries from October 1, 2018 - October 31, 2018
Research connects psychological factors and the immune system
Thursday, October 18, 2018 at 1:10PM Menzies Foundation: The following story is from our publication Taking the lead: 40 stories of impact.
Professor Adrian Liston is leading the way in immunology research overseas. He was awarded the 2006 NHMRC Menzies Fellowship, which allowed him to work at internationally-renowned labs through the University of Washington in Seattle, where he continued his groundbreaking research into controlling immune activation. He now runs his own lab in Belgium, where he works on solutions for patients with rare immune disorders that pharmaceutical companies don’t investigate. He simultaneously works on trying to understand why the regulatory cells actually work, and what’s different about these cells when they’re in different organs.
Since establishing his lab, Prof Liston and his team have made regular noteworthy findings, including one that links mental health with the immune system. He was able to ‘seize the moment’ and test a hypothesis from a ‘natural experiment’ during an outbreak of gastro that occurred when the water system was accidentally contaminated in two small towns outside Antwerp.
“The hypothesis linking mental health with the immune system had been tested successfully on mice,” Prof Liston explains. “But it hadn’t been tested on humans. It’s only because we were able to take advantage of this experiment of nature—the synchronised infections— that we were able to test the hypothesis.
"Our testing showed that individuals who had high levels of depression at the time of the infection had a different immune response to those who didn’t. The results showed that the depression-immunity link wasn’t something in the mind, it is due to actual changes in the blood that gives depressed or anxious people a different immune system response.
"Even years later, among people whose mental health had improved since that original time of infection, they still had ongoing complications because they got hit with an infection at a point where they had a lot of depression or anxiety.”
Liston lab Golden Pipette won by Dr Carly Whyte
Tuesday, October 16, 2018 at 3:39PM 
Congratulations to Dr Carly Whyte, for winning the Golden Pipette!
Carly won the Golden Pipette for her mind-boggling data on how the cellular source of IL-2 profoundly alters the impact of this key cytokine on the cells around it. Data to be published, as soon as we understand it!
Carly will be moving over to the Babraham in January. Will the Golden Pipette be won back by team Leuven in time? Or will Cambridge take ownership of this proud trophy?
Golden Pipette, immunology Our immune systems are incredibly diverse. How much of that diversity is due to our genes?
Tuesday, October 16, 2018 at 2:38PM Each of our immune systems acts a little bit differently. Environmental factors have an impact, but so do our genes. A team of researchers in Leuven went looking for links between more than 10 million genetic variations and more than 50 immunological traits. Their findings help to explain why some people have a higher risk for immune diseases than others.
Our immune systems are molded by our unique genetic make-up. Add to that a complex mix of environmental drivers, and you get an enormous functional diversity. From an evolutionary point of view, this diversity is essential to minimize the chance that a pathogen could wipe out an entire population.
But the flip-side is that we’re also greatly diverse when it comes to susceptibility or resistance to a broad range of diseases – not only those with an obvious immunological component, such as autoimmunity, allergy, inflammation and cancer, but also those with a more indirect link to immune-deregulation, such as cardiovascular, metabolic and neurological diseases.
A genome-wide survey
While scientists have studied the links between genetic variations and a whole range of different diseases, the characterization of this “genotype-phenotype relationship” for the immune system itself has received far less attention.
That is why a team of scientists led by An Goris (KU Leuven) and Adrian Liston (VIB-KU Leuven) undertook a large genetic study with almost 500 participants. In a so-called genome-wide association study, or GWAS, they probed more than 10 million genetic variations, spread out across the genome, for links to 54 different traits relevant to adaptive immunity. This allowed the researchers to determine which genetic variants were, for example, typical for people with high or low levels of different pro- or anti-inflammatory cytokines.
“We found eight previously unknown associations,” says An Goris, lead geneticist of the study. “The strongest connection was for a genetic variant present in only 2% of the study participants.” All of the identified genetic associations provide important biological insights into what drives variation in our immune systems.
This is only the tip of the iceberg, according to Goris: “What we know now, explains about 10% of the variation, but we are still in the initial discovery phase. There might be many more genetic variants—including relatively rare ones—that affect our immune response and thus our susceptibility to certain diseases.”
Helping to map disease risk and refine treatment
Mapping how genetic variants affect immune function will not only help us understand disease mechanism better, it should also help to refine treatment options.
“The clearest example is the clinical implication offered by genetic variation in the RICTOR gene,” explains Adrian Liston, lead immunologist on the study. “We now know that RICTOR changes the production of a cytokine called IL-4, providing a new therapeutic target for treatment of autoimmune diseases and asthma.”
In many cases, the effects are more subtle and indirect, adds Liston: “Most people will carry dozens of genetic variants that may skew the immune system in a particular direction. This accounts for part of the reason why different people have different risks for immune diseases, but we are much more than the sum of our genes.”
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Lagou et al. 2018 Cell Reports. 'Genetic architecture of adaptive immune system identifies key immune regulators'.
Liston lab, genetics, immunology 