2017 BIS annual meeting, November 24

The 2017 BIS annual meeting will be themed around "immune regulation". This year we will have four parallel sessions in the morning, each with a distinct immunological focus: fundamental immunology, clinical immunology, tumour immunology and neuroimmunology.

The afternoon will feature a joint session, with a plenary talk (Professor Gita Stockinger, Crick Institute, UK) and four keynote talks, one of each of the morning topics:

Anne Puel (France) on clinical Immunology 
Denise Fitzgerald (UK) on neuroimmunology

Gabriele Bergers (Belgium) on tumour Immunology

Anne Dejean (France) on fundamental Immunology

Registrations and abstract submissions are now open:

https://gbiomed.kuleuven.be/english/research/50000698/bis-annual-meeting

New insights in genetic defect allow prevention of fatal illnesses in children

A team of scientists led by prof. Adrian Liston (VIB–KU Leuven) and prof. Isabelle Meyts (UZ Leuven – KU Leuven) were able to characterize a new genetic immunodeficiency resulting from a mutation in a gene named STAT2. This mutation causes patients to be extremely vulnerable to normally mild childhood illnesses such as rotavirus and enterovirus. Prof. Liston’s comprehensive analysis of the genetic defect allows clinicians to provide children with the proper therapies before illnesses prove fatal. The findings of the research have been published in the Journal of Allergy and Clinical Immunology.

Recent advancements in technologies and tools now make it possible for researchers to identify extremely subtle defects of the human immune system. In the past, many patients with “hidden” immunodeficiencies, or defects that were not obvious from the outset, often become extremely ill or die before their genetic disorders are diagnosed. Prof. Liston and his lab were able to identify a gene mutation causing an immunodeficiency that can be fatal during childhood, enabling children to be diagnosed, monitored and preemptively treated for the disorder.

Immunodeficiency disorders are not rare

Ranging from disorders as severe as the well-known “bubble boy” to nearly impossible-to-detect ‘hidden’ defects, immunodeficiencies are more common than scientists previously thought. Immunologists and geneticists have only just begun to scratch the surface when it comes to defining these latter types of immune disorders, which can be specific enough to make sufferers highly susceptible to just one or two types of diseases.

Prof. Adrian Liston (VIB-KU Leuven): “I wouldn’t be surprised if, when we finally do complete the identification of all genetic immunodeficiencies, we discover that up to 1 in 100 children are affected. The ‘hidden’ ones are especially insidious, because they do not present as obviously as other genetic immune disorders. In our study, one of the patients did unfortunately die before a diagnosis could be made. The other patient is alive and well, and now that she has been diagnosed, she is being carefully watched. We can do something about most immunodeficiencies – if only we can identify them.”

Severe common illnesses may signal immune disorder

Prof. Meyts, lead clinician for the patients, stresses the importance of assessing the severity of childhood illnesses on the part of parents, suggesting that parents look for helpful information online and raise the possibility of a potential genetic immunodeficiency with a pediatrician.

Prof. Isabelle Meyts (UZ Leuven – KU Leuven): "When an otherwise healthy child experiences extremely severe infection with a common pathogen, like influenza or the chickenpox virus, or whenever a child is particularly vulnerable to infection with a single pathogen, an underlying defect in the immune system is likely. Likewise, a family history of a child succumbing to infection should alert the family and the clinician. Identifying the causative gene defect allows for genetic counseling of the family and for preventive measures to be taken."

Unraveling ‘hidden’ immunodeficiencies

The potential future avenues for this research are numerous and extremely relevant to current medicine. Prof. Liston’s lab has developed a unique immune phenotyping platform and gene discovery program that can help identify previously unknown immune system defects and inflammatory diseases, leading to novel new treatments that can be administered in a timely way.

Prof. Adrian Liston: “We seek to identify every possible cause of genetic immunodeficiency so that every child displaying warning signs can be tested and treated before it is too late.”

Shaping the human immune system

In the current issue of Trends in Immunology, we synthesize the latest literature on "population immunology", on the nature of variation in the immune system and our current understanding of the relevant drivers. 

Read: Liston, Carr and Linterman (2016). "Shaping variation in the human immune system". Trends in Immunology. 

Niet genen bepalen immuunsysteem maar omgeving

De Morgan, Sara Vandekerckhove 30-Sept, pg13

Iedereen heeft een uniek immuunsysteem. Maar hoe die 'witte soldaten' er uitzien, hangt grotendeels af van onze omgeving en niet van onze genen. Belgische onderzoekers proberen nu de hele immuuncode te ontrafelen.

"We stappen steeds meer af van het simplistische idee dat er slechts één type immuunsysteem bestaat", zegt Adrian Liston, hoofd van het VIB-KU Leuven Laboratorium voor Translationele Immunologie. Samen met twee andere immunologen gaf ze in een review in Trends in Immunology haar visie op de nieuwe inzichten erover.

Elke mens erft een uniek genenpakket dat ons helpt om infecties te overwinnen en dat bepaalt hoe ons immuunsysteem eruitziet. Maar recent onderzoek heeft nu uitgewezen dat niet die genen, maar onze geschiedenis, omgeving en levensstijl voor 60 tot 80 procent verantwoordelijk zijn voor de verschillen tussen immuunsystemen.

Drie belangrijke factoren bepalen mee hoe goed of slecht je reageert op allerlei bacteriën en virussen.

1. Infecties

De meeste verschillen tussen mensen als het over het immuunsysteem gaat, zijn te wijten aan langdurige infecties. Loopt iemand herpes of gordelroos op, dan heeft dat een enorm effect op de 'witte soldaten'. De wisselwerking tussen het virus en het immuunsysteem verandert langzaam de cellulaire samenstelling ervan en maakt het meteen ook gevoeliger voor dat specifieke virus.

Bovendien maakt het je meteen ook vatbaarder voor allerlei andere virussen. Bij mensen die niet geïnfecteerd raken, vinden die veranderingen niet plaats. Hun immuunsysteem blijft door de jaren heen relatief stabiel.

2. Leeftijd

Vanaf een bepaalde leeftijd slaat het immuunsysteem weer 'op hol'. Leeftijd speelt een belangrijke rol in de evolutie ervan. Waarom precies hebben onderzoekers nog niet kunnen achterhalen, maar het is wel bewezen dat het immuunsysteem anders reageert op bedreigingen van buitenaf naarmate we ouder worden.

Dat heef te maken met de thymus of zwezerik, een orgaan dat verschrompelt na de puberteit, en vervolgens geen cellen meer produceert die net infecties helpen bestrijden. Eens de thymus het laat afweten, word je sneller ziek.

3. Omgeving en levensstijl

Onderzoek bij mensen die samenleven heeft aangetoond dat de omgeving en de levensstijl een groot effect hebben op de levensstijl. Luchtkwaliteit, voeding, stress, slaappatronen hebben een grote impact op hoe goed je gewapend bent tegen virussen en bacteriën. Koppels die samenwonen hebben een gelijkaardig immuunsysteem.

Where You Live Shapes Your Immune System More than Your Genes

Cell Press press-release:

Like fingerprints, immune systems vary from person to person. And while we all inherit a unique set of T cells and B cells from our parents, recent studies have found that our environment—like where and with whom we live—is responsible for 60% to 80% of the differences between individual immune systems, while genetics account for the rest. In a Review published September 29 in Trends in Immunology, three immunologists discuss the emerging science of what shapes our immune systems and how it might be applied.

“Just like it took a while to crack the genetic code, we’re finally starting to crack the immune code, and we’re shifting away from the simplistic idea that there is only one type of immune system,” says lead author Adrian Liston, head of the VIB Translational Immunology Laboratory in Belgium. “Diversity isn’t just programmed into our genes-- it’s programmed into how our genes respond to the environment.”

Long-term infections are responsible for most of the differences between individual immune systems. For example, when a person has herpes or shingles, the virus has more opportunities to interact with the immune system. These interactions slowly change the cellular make-up of their immune system and make it more sensitive to that specific virus, but also easier for other infections to slip past its defenses. People without these infections don’t experience these cellular changes, and even with the occasional cold or fever, their immune systems stay relatively stable.

The exception is when a person is elderly. Researchers haven’t determined exactly why age plays a major role in making our individual immune systems more unique, but they have shown that aging changes how our immune system responds to threats. As we get older, an organ called the thymus gradually stops producing T cells, which are made to help to fight off infection. Without new T cells, older people are more likely to get sick and less likely to respond to vaccines.

“A lot of diseases that we associated with aging have an inflammatory component, which suggests there is likely immune involvement,” says Michelle Linterman, a researcher at the Babraham Institute and co-author of the review. “Understanding how the immune system changes with age is going to be hugely important for treating age-related diseases in the future.”

 Differences can be overcome, however; studies of people living together have shown that air quality, food, stress levels, sleep patterns, and lifestyle choices had a strong combined effect on our immune responses. For example, couples who cohabitate have more similar immune systems compared to the general public.

Liston and his collaborators, Linterman and Edward Carr of the Babraham Institute, would next like to explore how changing our environment could purposefully shape our immune system and potentially affect our health. “In order to tinker with the immune code, we first need to really understand the influences that shape the immune system,” says Liston. “That’s why it’s actually great that environment is more important than genetics, because we can play with environment.”

Read: Liston, Carr and Linterman (2016). "Shaping variation in the human immune system". Trends in Immunology. 

Understanding variation in the human immune system

My talk from the recent Eppendorf Young Investigator Award ceremony on variation in the human immune system.

Regulatory T cell mini-symposium

Leuven, October 14 2016

Hosted by the laboratory of Adrian Liston (VIB/KUL)

Regulatory T cells set the threshold between immunity and tolerance. At this mini-symposium, international experts will present the latest research on regulatory T cell biology, and how these cells can manipulate autoimmunity and cancer. 

We will also have Karin Dumstrei, Senior Editor at EMBO for immunology and neuroscience, to give advice to students and post-docs on successful navigation of the publication process.

Abstract submissions are encouraged from students and post-docs. Two will be selected for a short presentation, and the rest will be candidates for the €100 poster prize. Abstract submission is needed by Sept 1!

For information and to register, please visit: http://liston.vib.be/treg-symposium/ 

JACI Editors' Choice

Online here

Promising new insights into ALS

VIB research marks new step in understanding neurodegenerative diseases

Research into amyotrophic lateral sclerosis (ALS) conducted by VIB-KU Leuven has led to interesting and unexpected conclusions. When scientists were investigating the relevance of the higher expression of the IP₃R2 protein in blood of ALS patients, the general expectation was that lowering the expression of this protein would have a protective effect on the affected motor neurons. But the exact opposite was true: IP₃R2 turned out to be a protector against the negative effects of inflammation during ALS. Even more, the same mechanism may also apply to other diseases, such as stroke and multiple sclerosis.

This research was conducted in the VIB Laboratory of Neurobiology, led by professors Ludo Van Den Bosch and Wim Robberecht (VIB-KU Leuven). Other laboratories involved include Adrian Liston’s Translational Immunology laboratory (VIB-KU Leuven), Jo Van Ginderachter’s Inflammation Research Center (VIB-Vrije Universiteit Brussel), UZ Leuven and the Brain Science Institute RIKEN in Japan. The study’s remarkable conclusions are published in the renowned scientific journal Human Molecular Genetics.

Protective receptor

ALS is a fatal and currently incurable neurodegenerative disease caused by the progressive loss of motor neurons and denervation of muscle fibers, resulting in muscle weakness and paralysis. In Europe, 2.7 out of every 100,000 people are diagnosed with ALS on a yearly basis. Around 10% of all cases are hereditary, 20% of which are caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). For this type of ALS, mouse models have been developed and were used in this VIB research project.

Prof. Ludo Van Den Bosch (VIB-KU Leuven): “In blood of sporadic ALS patients, as well as in models of chronic and acute neurodegeneration, there is a significantly higher expression of the intracellular receptor IP₃R2. When we removed the gene encoding IP₃R2, the ALS mice didn’t just die quicker, we also saw systemic inflammation and increased expression of certain cytokines, proteins that plays an important role in the immune system. As a consequence, we conclude that doing the opposite, which is increasing the amount of IP₃R2, is a protective response. Not only for ALS, but also for other neurogenerative diseases.”

An unexpected twist

The research process is a prime example of good science, where no hypothesis whatsoever pre-determines the outcome. Although the scientists expected that deleting the gene encoding IP₃R2 which is responsible for the release of calcium from intracellular calcium stores would have a positive effect on the survival of motor neurons, the study proved the opposite: IP₃R2 deletion had a negative effect on the survival of the ALS mouse model.

Prof. Ludo Van Den Bosch (VIB-KU Leuven): “The negative effects of IP₃R2 removal in other cell types seem to outweigh the potential benefits of removing IP₃R2 in motor neurons. In the case of unexpected findings like this, a researcher has two options: to stop the project, or to dig deeper into the problem. The last strategy is the most challenging one, as the outcome is uncertain. But, in this case, it has yielded interesting new insights, supported by our data.”

Next steps

The VIB lab is currently involved in a new ALS study in collaboration with the Stem Cell Institute Leuven (SCIL) and supported by the Belgian ALS Liga. Focusing on different cell types derived from skin fibroblasts of ALS patients, scientists are looking for aberrations in their calcium metabolism. The research into the role of the IP₃R2 can serve as an important foundation, as it helps to strengthen the scientific community’s understanding of the mechanisms that may protect motor neurons.

Prof. Ludo Van Den Bosch (VIB-KU Leuven): “We have now proven that some aspects of inflammation could play an important role in the disease, which could eventually open new therapeutic options for patients. But if we really want to cure ALS, we need to understand all the ins and outs of ALS on the patient’s cellular level. Studies like ours are crucial pieces of this complex puzzle that we need to solve before we can develop a successful therapy.”

Read more: Staats, et al., Genetic ablation of IP₃ receptor 2 increases cytokines and decreases survival of SOD1^G93A mice. Human Molecular Genetics. 2016.

Journal club: Transmissible cancer may not be so rare

Cancer is a disease of our own cells gone wrong. Normally our cells work in harmony with each other, taking cues from each other as to when to proliferate, when to differentiate and when to die. In cancer, mutation takes away this level of regulation, leaving a "selfish cell" that ignores all of these signals and proliferates uncontrollably, even to the point of killing the host.

There have been a handful of rare cases where cancers can actually physically cross-over from one individual to another, such that the second individual is actually growing cancer cells that are not self, but are fully derived from the original host. This has been seen in a few human cases as well as well-described transmissible cancers in Tasmanian Devils and dogs. There was even a recent case study that suggests a tapeworm cancer crossed over into the host. In general, however, it is thought that this type of event is going to be exceptionally rare. Even ignoring the protective effect of our immune system killing foreign cells, it is not like cells from one individual can just float through the air to colonise another. Except, of course, under the water.

A paper just published in Nature looks for transmissible cancers in mussels and clams and finds three examples of cancer cells from one individual clam or mussels infecting and growing in other indiviudals of the same, or even different, species. With high population densities and water flow acting to directly transfer cancer cells, it is probably that transmissible cancers are actually a common feature in many marine environments.

Nature 2016, in press. Widespread transmission of independent cancer lineages within multiple bivalve species. Metzger, Villalba, Carballal, Iglesias, Sherry, Reinisch, Muttray, Baldwin, Goff.