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Entries in Liston lab (241)

Thursday
Mar102016

New study provides insight into Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disease caused by macrophage activation. Watch "Max the Angry Macrophage":

In patients with the primary (genetic) form of the disease, the underlying cause of illness is a defect in CD8 T cells which makes them inefficient at clearing viruses. The connection between this defect and the disease onset has, however, been unclear. 

In a new study from the Translational Immunology laboratory, we used a mouse model of HLH to dissect the mechanism leading to disease. We found that the CD8 T cells try to overcome their defect in anti-viral killing by becoming more and more activated. One consequence of this activity is that they start consuming a key cytokine in the blood, IL-2. IL-2 is necessary for the survival of regulatory T cells, the key cell type for calming down a hyper-active immune system. When the activated CD8 T cells consumed all of the IL-2, the regulatory T cells started dying off due to IL-2 starvation, leading to excessive inflammation. The same lack of regulatory T cells was found in HLH patients, indicating that this is the mechanism driving inflammatory disease in patients. These results identify a new therapeutic target for HLH patients.

 

Humblet-Baron S, Franckaert D, Dooley J, Bornschein S, Cauwe B, Schönefeldt S, Bossuyt X, Matthys P, Baron F, Wouters C, Liston A. 'IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis.' J Allergy Clin Immunol. 2016 Mar 3. pii: S0091-6749(16)00115-9. doi: 10.1016/j.jaci.2015.12.1314.

Friday
Mar042016

Thursday
Feb182016

...and yet we still have kids

Great job by PhD student in the lab, Dean Frankaert, on VTM news last night - Belgian TV star! 

Our research on the shaping of the human immune system has also had a lot of international media attention the last few days. New Scientist has a great article on the work, and I have to give a special call out to the Daily Mail, since the journalist who wrote this article was savvy enough to ask about Pathogen-Associated Molecular Patterns. It is also fun to read quotes from yourself in German or Italian. My personal favourite, however, would have to be the Australian media:

If you had to rate how hard parenting is, where would you put it on a scale from "perfectly fine" to "worse than suffering from extreme vomiting and diarrhoea"?

If you answered "somewhere in between", you might be surprised to hear the truth is even more extreme – because new research has discovered that parenting hits your immune system harder than travellers' gastroenteritis.

Yes, that's right – raising children is as hard on your body as projectile vomiting in a foreign airport.

It's funny because it is true.

Wednesday
Feb172016

Een kind verandert alles, vooral je immuunsysteem

Voor welke ziektekiemen we vatbaar zijn, hangt af van onze genen, ons gewicht en hoe goed we ons in ons vel voelen. Maar het belangrijkste effect hebben kinderen.

Het immuunsysteem beschermt ons tegen ziekten. Tegen welke ziektekiemen het lichaam precies gewapend is, verschilt sterk van persoon tot persoon. Een onderzoeksteam van de Leuvense tak van het Vlaams Instituut voor Biotechnologie en het Britse Babraham Institute vond in het bloed van 670 proefpersonen aanwijzingen dat mensen elkaars immuunsysteem sterk beïnvloeden. Adrian Liston leidde het onderzoek.

Professor Liston, veel jonge ouders worden ziek, zodra hun kindje naar de crèche gaat. U hebt vastgesteld dat een kind grootbrengen het immuunsysteem van de ouders verandert. Ten slechte?

‘Niet per se. We zien dat personen die samenwonen, op den duur immuunsystemen hebben die sterk op elkaar lijken. Terwijl voorheen de ene misschien zeer vatbaar was voor bacteriële ziektes en minder voor virale aandoeningen, kan hij van de ander de weerbaarheid tegen virussen overnemen. Hij is dan voortaan wel, net als zijn partner, kwetsbaar voor bacteriën. Het risico op bepaalde ziektes neemt dus door het samenleven toe, het risico op andere dan weer af.’

‘Samen een kind grootbrengen blijkt dat effect te versterken. Ons onderzoek bij kinderen en volwassenen uit België en het Verenigd Koninkrijk toont aan dat een kind voor je immuunsysteem zelfs een belangrijkere rol speelt dan je genen, je gewicht, je geslacht of hoe je je voelt.’

Hoe komt dat?

‘Als je gedurende tien seconden kust, wissel je zo’n 80 miljoen bacteriën uit. Op een gegeven moment draag je dus dezelfde bacteriën als je partner en daar reageert je immuunsysteem op. Als twee volwassenen samen voor hun kindje zorgen, wisselen ze ook via het kindje bacteriën en virussen uit.’

Als de ene ouder ziek wordt, is de ander dus ook buiten strijd?

‘Ja. Maar dat is op zich niet zorgwekkend bij personen die voor de rest gezond zijn.’

‘In een rusthuis is dat iets anders. De bewoners hebben geen intieme relatie met elkaar, maar ze wonen wel allemaal samen. Mogelijk lijken hun immuunsystemen sterk op elkaar en is de groep zeer vatbaar voor uitbraken, bijvoorbeeld van griep. Dat zouden we graag in detail verder onderzoeken.’

 

Courtesy of De Staandard

Tuesday
Feb162016

Think twice before you have kids!

Prof Michelle Linterman, co-lead author on our recent study on the effect of children on the immune system, has been hitting the airwaves today:

Interested? Listen here for a recap of the BBC World Service (conversation runs from 08.53-12.40), or here for the Today show (45.07).

Monday
Feb152016

Share a child? Then your immune systems look pretty similar too

The human immune system is shaped by family and household

Raising a child together has a greater effect on your immune system than the seasonal 'flu vaccine or travellers' gastroenteritis, a study by researchers at the VIB in Belgium and the Babraham Institute in the UK has found.

The research took a detailed look at the immune systems of 670 people, ranging from 2-86 years of age, to understand more about what drives variation in our immune systems between individuals. From an assessment of the effects of a range of factors, including age, gender and obesity, one of the most potent factors that altered an individual's immune system was whether they co-parented a child. Individuals who lived together and shared a child showed a 50% reduction in the variation between their two immune systems, compared with the diversity seen in the wider population. 

Dr Adrian Liston, a researcher at the VIB and University of Leuven who co-led the research said: "This is the first time anyone has looked at the immune profiles of two unrelated individuals in a close relationship. Since parenting is one of the most severe environmental challenges anyone willingly puts themselves through, it makes sense that it radically rewires the immune system - still, it was a surprise that having kids was a much more potent immune challenge than severe gasteroenteritis. That's at least something for prospective parents to consider - the sleep deprivation, stress, chronic infections and all the other challenges of parenting does more to our body than just gives us grey hairs. I think that any parents of a nursery- or school-age child can appreciate the effect a child has on your immune system!"

Every individual has a unique immune system, something which can be visualised as a unique location in “immunological space”. Our immune systems are also dynamic, with minor differences on a day-to-day basis. The biggest shapers of our immune systems are age, with a gradual ageing of the immune system over time, and cohabitation, where having a child together causes the unique immune signature of each individual to come much closer. Image produced by Dr Carl 

Participants in the study were assessed over a period of three years. Regularly monitoring their immune systems showed that the individuals maintained a stable immune landscape over time, even after their immune systems were triggered into action by the seasonal ‘flu vaccine or gastroenteritis. The researchers found that following immune challenge, our immune systems tend to bounce back to the original steady state, demonstrating the elastic potential of our immune system.

In assessing the effect of other factors on the immune system, such as age, obesity, gender, anxiety and depression, the study found that age is a crucial factor in shaping the immunological landscape, agreeing with the age-related decline seen in response to vaccination and reduced resistance to infection.

Dr Michelle Linterman, a researcher at the Babraham Institute who co-led the research said: “Our research shows that we all have a stable immune landscape which is robustly maintained. What is different between individuals is what our individual immune systems look like. We know that only a small part of this is due to genetics. Our study has shown that age is a major influence on what our immune landscapes look like, which is probably one of the reasons why there is a declining response to vaccination and reduced resistance to infection in older persons.”

The research is published by the leading international journal Nature Immunology and was funded by two European Research Council grants. Dr Michelle Linterman and her group at the Babraham Institute are supported by the Biotechnology and Biological Sciences Research Council.  Dr Adrian Liston and his group are members of the VIB and University of Leuven, in Belgium.


Publication: Carr et al. (2016) The human immune system is robustly maintained in multiple equilibriums by age and cohabitation. Nature Immunology

Saturday
Jan092016

Friday
Jan012016

Francqui Chair award

Wednesday
Dec162015

European Research Council funding for the laboratory

VIB press release:

The European Research Council (ERC) has awarded 4 VIB scientists a consolidator grant: Kevin Verstrepen (VIB/KU Leuven), Adrian Liston (VIB/KU Leuven), Mohamed Lamkanfi (VIB/UGent) and Daniël Van Damme (VIB/UGent). These 'consolidator grants' are rewarded to scientists (PhD 7-12 years) who already showed that they are able to run their own lab. The European Research Council's grant allows them to anchor the start of a high risk/high gain program, feasible through this recognition of nearly 2 Mio€ per scientist.


ERC grants
Right from the start, VIB recognized the importance of ERC for its own mission, given our obvious synergy at the science policy level:
- Frontier research
- Excellence as the only selection criterion
- Bottom-up, all fields
- Support for the individual scientist
- International peer review

Every year VIB encourages group leaders to apply for  ERC grants and supports them when they do. With these four new ERC grants VIB has reached the impressive number of 34 ERC-grants.

Recognition for four VIB researchers

Adrian Liston (VIB/KU Leuven) who will develop new molecular tools to study the immune system in the brain during neurodegenerative disease, says: “This ERC grant offers me an exciting opportunity to start a major initiative in looking at the interaction between the immune system and the brain.”

Kevin Verstrepen (VIB/KU Leuven) will investigate whether cells can somehow remember past experiences, and whether such past experiences influence how cells respond to their current environment.  In other words, he wants to find out whether living cells, including simple cells such as microbes as well as more complex cells in animals, have a basic form of memory (that is obviously more simple and restricted from the kind of memory associated with a brain in higher animals and humans). His reaction: “The ERC funding provides a fantastic boost to our research, because the amount of money we receive from Europe is substantial enough to recruit a complete team of scientists to pursue a new line of research that really pushes the boundaries of our current knowledge of biology.”  

Mo Lamkanfi (VIB/UGent): ‘Our ERC project will map the broad communication between inflammasomes and the diverse programmed cell death mechanisms in immune cells. This will help to define novel approaches to treat autoinflammatory and -immune diseases by converting pathological cell death into non-inflammatory responses.’

Daniël Van Damme (VIB/UGent): “Achieving an ERC grant consolidates my independent research position within the VIB Department of Plant Systems Biology and Ghent University. It provides me with the means to unravel why the process of endocytosis evolved differently in plants compared to animal and yeast cells.” With his T-REX project he will combine ultrastructural analysis of the main endocytic adaptor complex in plants with proteomic identification of its endocytic cargo and functional cell biological analysis of its subunits.

--

If anyone is interested in my advice on applying for ERC grants, here are the hints I wrote in 2010 after going through the ERC Start grant process.

Wednesday
Dec092015

Dr Karel-Lodewijk Verleysen Prize

Professor Adrian Liston has been selected for the Prijs Dr. Karel-Lodewijk Verleysen for his work on the development of a safe and effective immune system. Professor Liston received his PhD from the Australian National University in Canberra, Australia, for seminal work on the role of the thymus in eliminating autoreactive T cells from the repoirtoire, a process known as immunological tolerance. His doctoral research identified defects in thymic tolerance as a key mechanism in the development of autoimmune disease.

Following his PhD in 2005, Professor Liston moved to the University of Washington in the United States of America in order to continue his research on T cell tolerance, performing some of the earliest experiments on the generation of regulatory T cells, a cell type that has come to dominate the field of autoimmunity in recent years.

Professor Liston was recruited to Belgium in 2009 by the VIB and University of Leuven, where he became a professor (hoofddocent) at the age of 28. In the last 6 years he has built up a laboratory of 15 researchers, dedicated to understanding the mechanisms of immune tolerance failure during autoimmunity and immunodeficiency.

Professor Liston has published more than 90 research papers, over a diverse set of topics in immunology and genetics and with publications in the top international journals such as Nature Immunology, Nature Medicine and Immunity. Of the many important findings, I would like to briefly highlight just four.

First, in collaboration with Cambridge University, Professor Liston identified a new cell type in 2011, the follicular regulatory T cell. This new cell type controls the strength of the antibody responses to vaccination, and is now thought to be important in diseases such as lupus.

Second, in 2012 Professor Liston’s research identified one of the key mechanisms that control the atrophy of the thymus with age. This reduction in the activity of the thymus is thought to be behind the poor vaccine responses of older persons. Professor Liston demonstrated that small non-coding RNA particles, known as microRNA, control the size of the thymus with age by altering the response to normal gut bacteria.

Third, Professor Liston has continued to work on the properties of regulatory T cells. In 2013 he published a seminal paper which systematically tested the signals that drive the life and death of regulatory T cells, identifying the key pathway that controls the quality of immune tolerance. This work is now being translated into immune therapeutics, where regulatory T cells are being seen as a high potential strategy to stop graft versus host disease.

Finally, Professor Liston is actively involved in the medical genetics of immune disorders. In the last few years Professor Liston has been working with clinicians at UZ Leuven to unravel the genetics behind patients with severe early-onset autoinflammation and immunodeficiency. This work has brought next generation sequencing into the diagnostic arena in immunology at UZ Leuven, and has identified several new immune disorders, such as the combined immunodeficiency and vasculopathy disorder caused by ADA2 mutation and several new genetic causes for immunodeficiency. Professor Liston is working hard to bring these advances in genetics into the standard diagnostic process, so that the genetic mechanism can inform on treatment options.

During his 6 years in Belgium, Professor Liston has received several major funding awards, including a Marie Curie Fellowship, a Juvenile Diabetes Research Foundation Career Development Award and a European Research Council Start Grant, bringing more than €3 million of international research funding into Belgium. He is a member of many national and international consortium and founded and directs the flow cytometry core facility in Leuven. Professor Liston is also active in science education and community outreach. For these contribution to medical research in Belgium, Professor Adrian Liston has been selected for the 2014 Prijs Dr. Karel-Lodewijk Verleysen.