Discovery of ‘new rules of the immune system’ could improve treatment of inflammatory diseases, say scientists.

Scientists at the University of Cambridge have discovered that a type of white blood cell - called a regulatory T cell - exists as a single large population of cells that constantly move throughout the body looking for, and repairing, damaged tissue.

This overturns the traditional thinking that regulatory T cells exist as multiple specialist populations that are restricted to specific parts of the body. The finding has implications for the treatment of many different diseases – because almost all diseases and injuries trigger the body’s immune system.

Current anti-inflammatory drugs treat the whole body, rather than just the part needing treatment. The researchers say their findings mean it could be possible to shut down the body’s immune response and repair damage in any specific part of the body, without affecting the rest of it. This means that higher, more targeted doses of drugs could be used to treat disease – potentially with rapid results.

It's difficult to think of a disease, injury or infection that doesn’t involve some kind of immune response, and our finding really changes the way we could control this response.

Adrian Liston

“We’ve uncovered new rules of the immune system. This ‘unified healer army’ can do everything - repair injured muscle, make your fat cells respond better to insulin, regrow hair follicles.  To think that we could use it in such an enormous range of diseases is fantastic: it’s got the potential to be used for almost everything,” said Professor Adrian Liston in the University of Cambridge’s Department of Pathology, senior author of the paper.

To reach this discovery, the researchers analysed the regulatory T cells present in 48 different tissues in the bodies of mice. This revealed that the cells are not specialised or static, but move through the body to where they’re needed. The results are published today in the journal Immunity.

“It's difficult to think of a disease, injury or infection that doesn’t involve some kind of immune response, and our finding really changes the way we could control this response,” said Liston.

He added: “Now that we know these regulatory T cells are present everywhere in the body, in principle we can start to make immune suppression and tissue regeneration treatments that are targeted against a single organ – a vast improvement on current treatments that are like hitting the body with a sledgehammer.”

Using a drug they have already designed, the researchers have shown - in mice - that it’s possible to attract regulatory T cells to a specific part of the body, increase their number, and activate them to turn off the immune response and promote healing in just one organ or tissue.

“By boosting the number of regulatory T cells in targeted areas of the body, we can help the body do a better job of repairing itself, or managing immune responses,” said Liston.

He added: “There are so many different diseases where we’d like to shut down an immune response and start a repair response, for example autoimmune diseases like multiple sclerosis, and even many infectious diseases.”

Most symptoms of infections such as COVID are not from the virus itself, but from the body’s immune system attacking the virus. Once the virus is past its peak, regulatory T cells should switch off the body’s immune response, but in some people the process isn’t very efficient and can result in ongoing problems. The new finding means it could be possible to use a drug to shut down the immune response in the patient’s lungs, while letting the immune system in the rest of the body continue to function normally.

In another example, people who receive organ transplants must take immuno-suppressant drugs for the rest of their lives to prevent organ rejection, because the body mounts a severe immune response against the transplanted organ. But this makes them highly vulnerable to infections. The new finding helps the design of new drugs to shut down the body’s immune response against only the transplanted organ but keep the rest of the body working normally, enabling the patient to lead a normal life.

Most white blood cells attack infections in the body by triggering an immune response. In contrast, regulatory T cells act like a ‘unified healer army’ whose purpose is to shut down this immune response once it has done its job - and repair the tissue damage caused by it.

The researchers are now fundraising to set up a spin-out company, with the aim of running clinical trials to test their findings in humans within the next few years.

The research was funded by the European Research Council (ERC), Wellcome, and the Biotechnology and Biological Sciences Research Council (BBSRC).

Reference: Liston, A. ‘The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program.’ Immunity, June 2024. DOI: 10.1016/j.immuni.2024.05.023

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In brief

• A single large population of healer cells, called regulatory T cells, is whizzing around our body - not multiple specialist populations restricted to specific parts of the body as previously thought.
• These cells shut down inflammation and repair the collateral damage to cells caused after our immune system has responded to injury or illness.
• Tests, in mice, of a drug developed by the researchers showed that regulatory T cells can be attracted to specific body parts, boosted in number, and activated to suppress immune response and rebuild tissue.
• Current anti-inflammatory drugs used for this purpose suppress the body’s whole immune system, making patients more vulnerable to infection.
• The discovery could lead to more targeted treatments, with fewer side-effects, for issues from lengthy COVID infections to autoimmune diseases like multiple sclerosis. Clinical trials in humans are now planned.

Nurturing a positive research culture

Write-up on our recent article on positive research culture:

Nurturing a positive research culture

A Fellow of St Catharine’s is sharing practical advice on how to nurture a positive research culture within a laboratory and across an organisation. Professor Adrian Liston (2023), Professor of Pathology at the University of Cambridge, has co-authored two articles in response to a new emphasis on the importance of research culture in the UK’s funding landscape. The first article has just been published in the journal Immunology & Cell Biology.

He said, “The choices made by the leadership of a lab or an organisation – intentionally or more often than not unintentionally – can determine their research culture. There are cultures where researchers operate in competition (what I would call a toxic culture) or, with a bit of luck, you may encounter more positive research cultures, which tend to grow organically from the kindness and integrity of team members. Over successive generations, researchers have perpetuated cultures that were linked to past achievements. Unfortunately this hasn’t weeded out negative tendencies, because some researchers can succeed in a toxic environment in spite of – rather than due to – that research culture. We need to take a more deliberate approach to establishing positive research cultures within our organisations.”

Prof. Adrian Liston in his laboratory

The new emphasis on research culture was clear in June 2023 when the four higher education funding bodies in the UK announced that the Research Excellence Framework 2029 will have an expanded definition of research excellence to encompass people, culture and environment. This is on top of the £30 million already announced by UKRI’s Research England in 2022 to enable higher education providers to develop and initiate activities that will enhance research culture across the sector. 

Professor Liston explained, “There has been a recent sea change in attitudes at the highest levels of government and funding bodies, who now accept that research excellence is not only fuelled by the quantity and quality of outputs, but also by people, culture and environment. Personally, this change is very welcome and I am excited that we now have a fresh opportunity to rethink the research cultures that we are perpetuating, break bad habits and nurture positive ones.

“If we want to replicate the advances seen in other areas of scientific practice in progressing research culture, it is vital that we share best practice, examples and mechanisms that benefit our field. I know from my own experience that an individual early career researcher might only have worked in two or three different research cultures before deciding how they want their own lab to operate. I hope these two articles offer a toolkit for others to draw upon and inspire further discussion about different aspects of research culture so we can harness the collective experience of labs and organisations across the world.”

Team members in Prof. Liston's research group

The first article in the pair identifies the actionable areas where organisations can create and reinforce a positive research culture:

• Aligning staff recognition to the organisation’s missions;
• Designing the organisation structure around the mission and the people;
• Building a respectful environment;
• Openness and transparency; and
• Equality, diversity and inclusivity.

Each area is accompanied by frameworks, examples and/or other resources for readers to review and adapt according to their organisation’s needs. While Professor Liston and his co-author Professor Denise Fitzgerald work on similar research themes and have chosen to publish with Immunology & Cell Biology, their arguments are relevant for other academic disciplines. For example, their argument for organisations investing their energies at all levels of the ‘respect pyramid’ rather than relying entirely on punitive actions against toxic behaviours like bullying and harassment:

“The most visible interventions for nurturing a respectful environment (punitive actions against toxic behaviour) should also be the rarest, in the same way that the hospital is the last resort in creating a healthy environment. Underpinning this “emergency care” should be strategic positive interventions, rolled out when environments are suboptimal but before they reach a critical stage (analogous to treatment by a family doctor). More pervasive still should be the underlying fabric of the organisation, supporting a culture of respect, with individuals, in particular those in leadership positions, taking personal responsibility for their interactions.”

The respect pyramid provides the basis for building a respectful environment

Reference 

Adrian Liston and Denise C. Fitzgerald. Nurturing a positive research culture within your organisation. Immunology & Cell Biology. 2024; 1–10. doi: 10.1111/imcb.12795

Harnessing our lived experience for science communication

Thanks to Nature Reviews Immunology for the chance to write about incorporating our lived experiences into effective science communication! A few tips on making your science communication effective and accessible to everyone:

First, find your passion! Reach out to the communities that you have connections to, and use a medium that you enjoy. You don't need to be an extravert to do public engagement! If you prefer to interact online, do so - there are audiences that want it. Content creation without any face-to-face interaction such as VirusFighter sci-comms too!

Second, harness your lived experience! Being slotted into a generic event that doesn't resonate with your life is a major turn-off. Using your identity in your comms builds the authenticity that audiences respond to, e.g. my efforts writing kids books, like Maya's Marvellous Medicine, are rooted in my life experience as a daddy.

Third, find collaborators with complementary skills. If you have a vision for an innovative outreach project, the talent is around you to make it happen! Those kids books needed artistic talent, via Sonia Agüera Gonzalez, our computer game needed coding expertise, via Simon Andrews, and our next project started after a chat in the pub revealed the talents of Yulia Lapko!

Finally, look to extend your reach! Taking a pro-active approach to inclusivity dramatically extends your impact. Look to reach the communities that are usually overlooked, such as Erica Tandori and her drive to make sciart accessible to the blind and low vision community through Sensory Science!

That's TV Cambridge interview

My interview on Sensory Science for That's TV Cambridge.

Key point: Science is for everyone, the benefits of science are for everyone, so science communication needs to be for everyone.

VirusFighter

VirusFighter at the Cambridge Festival! The kids had a blast, maybe try it yourself? Want to be in the driving seat as UK Prime Minister during the COVID pandemic? Make real-time decisions based on the information available and watch the pandemic play out. Or maybe you are keen to genetically-engineer a virus to prevent the UK being overrun by invasive wombats? Give it a shot!

Sensory Science on the BBC

Cambridge University sensory-science art for people with sight loss

By Kate Bradbrook and Helen Burchell

BBC News, Cambridgeshire

Art exploring science and created for people with sight loss is on show as part of a festival organised by Cambridge University.

Sensory Science, at St Catharine's College, is part of the Cambridge Festival, which explores aspects of research carried out at the university and is open to the public.

Scientists at the Department of Pathology worked with local artists to create pieces to communicate science.

The festival runs until 28 March.

Sensory Science is the brainchild of Dr Erica Tandori, a low-vision artist based in Melbourne, Australia.

She was diagnosed with Stargardt disease - a form of macular dystrophy - when she was 23, and trained in creative arts and scientific communication.

"I'm an artist that's absolutely in love with science," she said.

"The whole idea of making things multi-sensory brings knowledge to life and makes it more accessible to everyone."

The pieces on show include lights and music and "is about all of us - cells and the immune system - and it should be available to all of us".

Together with Prof Jamie Rossjohn from Monash University in Australia, Dr Tandori saw the need for science communication to reach the blind and low-vision community.

She also worked with Prof Adrian Liston, professor of pathology at Cambridge University, who said: "The really unique aspect about this particular event is that we're really going for a multi-sensory approach.

"This involves not just the visual but auditory soundscapes, tactile maps, smell - other ways of communicating concepts.

"The aim is to make this as inclusive as possible.

"Using multiple senses is obviously a huge advantage if you want to include the blind and low-vision community."

Dr Julia Johnson, from Anglia Ruskin University, worked on the project with art and pathology students.

"We're looking at art's value in addressing some of the topics here," she said.

"We're thinking about how art can act as a communication tool for engaging audiences.

"Through a very sensory and tactile approach, young people and low-vision audiences can understand more about scientific models."

Read the article online here

Sensory Science

Liston-Dooley lab at the Cambridge Festival!

Our lab is gearing up for the Cambridge Festival! A lot of amazing activities, with something for everyone, so hopefully everyone in Cambridge can come and join at least one of these.

First of all, for our youngest visitors come along to a book reading of our kids books "Maya's Marvellous Medicine" and "Battle Robots of the Blood". We'll have some colouring in too, to keep them busy.

For kids a little older, Family Day at Pathology has a ton of activities! Our lab is hosting a display of "VirusFighter". See how your kids would have done as PM during the pandemic, or test whether they can successfully engineer a bioweapon to stop an invasion of wombats! (They can also play online now!)

 For all ages, we have a real treat, Sensory Science. This is a fantastic program that uses multi-sensory art to communicate the science of pathology. Honestly, everyone should come and experience this exhibit at St Catharine's College, the teams have put in so much work into their art piece. Our lab has coordinate the program and is exhibiting new art on neuroinflammation and cancer formation. We are also hosting the amazing Dr Erica Tandori, who started the Sensory Science movement back in Australia, and specialises in making science communication accessible to the blind and low vision community.

Finally, adults interested in the immune system are welcome to join my public seminar on how diversity shapes our immune responses!

Congratulations to Jasmine Hughes!

Congratulations to Jasmine Hughes for her Cook Society Award for dedicating herself to social justice, equality and strengthening the campus community, during her time at Duke University! I'm glad to say she is keeping up the focus during her PhD here at the University of Cambridge!

New positions in the lab!

We are recruiting two new positions, a Postdoctoral Research Scientist and a Research Laboratory Technician, to join our lab! 

This translational research project aims to develop novel technologies for treating neuroimmunology into clinic-ready molecules. You will contribute to the optimisation of therapeutics for brain delivery to patients, as part of the commercialisation pathway for a recently developed neuroinflammation treatment (Yshii et al, Nature Immunology 2022). The laboratory is an inclusive, international and diverse team, supportive of your personal and career development. A positive approach to kind and collaborative interactions with the team is essential! You will benefit from the collaborative and collegial environment of the laboratory, and potential career growth opportunities within the laboratory and within the developing spin-off company Aila Biotech are possible for a successful post-holders. 

The Post-doctoral Scientist post would be suitable for a new PhD graduate who is motivated to develop new skills in both neuroimmunology and in commercialisation. The post is designed to result in scientific publications and patent applications. Post-doctoral Scientist's apply here.

The Research Laboratory Technician post would be suitable for a candidates from a range of backgrounds, such as experience in animal handling, or a basic laboratory experience, or a Masters-level degree in immunology, neuroscience, or a related field. Applicants are not expected to enter with the full range of these skills or experiences. Research Laboratory Technician's apply here.