Researchers at the University of Cambridge have discovered that regulatory T cells form a single, mobile population that patrols the entire body to repair tissue damage. This new understanding could revolutionize the treatment of a range of diseases by enabling targeted immune suppression and tissue regeneration to specific organs, improving the efficacy and speed of treatment. The research team is now working towards clinical trials to further explore these findings.
Researchers at the University of Cambridge have discovered that regulatory T cells patrol throughout the body to repair tissues, paving the way for targeted treatments for a range of diseases.
Researchers at the University of Cambridge have discovered that regulatory T cells, a type of white blood cell, form a single large population that continuously circulates throughout the body to seek out and repair damaged tissue.
This contradicts the previous idea that regulatory T cells exist as specialized populations restricted to specific sites in the body. This discovery has implications for the treatment of a variety of diseases, because almost every illness or injury stimulates the body’s immune system.
Current anti-inflammatory drugs treat the whole body, not just the area that needs treatment. The researchers say this discovery means they may be able to suppress the body’s immune response and repair damage in specific areas without affecting other parts of the body. This means higher doses and more targeted drugs could be used to treat the disease, with the potential to see faster results.
The study’s lead authors, Professor Adrian Liston and Dr James Dooley, use a microscope to track anti-inflammatory regulatory T cells as they move through tissue. Photo credit: Louisa Wood/Babraham Institute
Unified healing power
“We’ve discovered new rules for the immune system. This ‘unified army of healers’ can do everything from repairing damaged muscles to making fat cells more responsive.” Insulin“This technique regenerates hair follicles, regenerates hair follicles, and it’s fantastic to think that it could be used for such a wide range of diseases – it has the potential to be used for almost any disease,” said lead author Professor Adrian Liston, from Cambridge University’s department of pathology.
To reach their findings, the researchers analyzed regulatory T cells in 48 different tissues in mice and found that the cells are not specialized or static, but rather migrate around the body to where they are needed. Their findings are published today in the journal Neurology. Immunity.
Regulatory T cells can travel from tissue to tissue via the blood. It takes the cells only a few minutes to travel through the body, but once in the tissue, they slow down and take an average of three weeks to leave the tissue. Credit: Equinox Graphics
“It’s hard to think of any disease, injury or infection that doesn’t involve some sort of immune response, and our discovery marks a sea change in how we regulate this response,” Liston said.
He added: “Now that we know that regulatory T cells are present throughout the body, we could, in principle, begin to target immunosuppressive and tissue regenerative therapies to single organs. This would be a major improvement over current therapies, which involve hitting the body with a sledgehammer.”
Drug development and clinical application
Using drugs they have designed, the researchers have demonstrated in mice that they can attract regulatory T cells to a specific part of the body, increase their numbers, and activate them to turn off the immune response and promote healing in just one organ or tissue.
“By increasing the numbers of regulatory T cells in target sites in the body, we can help the body more effectively repair itself and manage the immune response,” Liston said.
Dr Oliver Barton, lead author of the study, uses spectral cytometry to analyse anti-inflammatory regulatory T cells from a range of tissues. Photo credit: Louisa Wood, Babraham Institute
He adds: “There are many diseases, including autoimmune diseases like multiple sclerosis and many infectious diseases, in which you want to shut down the immune response and start a repair response.”
Most symptoms of infectious diseases such as COVID are virus “This happens when the body’s immune system attacks the virus, not the virus itself. Once the virus has peaked, regulatory T cells are supposed to shut down the body’s immune response, but in some people this process isn’t very efficient, which can lead to ongoing problems. This new discovery means that it may be possible to use drugs to shut down the immune response in a patient’s lungs, while the immune system in other parts of the body continues to function normally.”
As another example, people who receive organ transplants must take immunosuppressants for the rest of their lives to prevent organ rejection because their body mounts a strong immune response to the transplanted organ, but this makes them highly susceptible to infections. This new discovery can help design new drugs that only suppress the body’s immune response to the transplanted organ, allowing the rest of the body to function normally and allowing patients to lead normal lives.
Most white blood cells attack infections in the body by triggering an immune response. In contrast, regulatory T cells act like a “unified healing army” whose purpose is to shut down immune responses after they have done their job and to repair tissue damage caused by them.
The researchers are currently raising funds to set up a spin-out company, with the aim of conducting clinical trials to test their findings in humans within the next few years.
Reference: “Tissue-resident regulatory T cell pools are shaped by transient multitissue migration and a conserved resident program” Oliver T. Barton, Oriane Bricard, Samer Tareen, Vaclav Gergelits, Simon Andrews, Laura Biggins, Carlos P. Roca, Carly White, Stephie Junius, Alexandra Blasic, Emanuela Pascueto, Magda Ali, Pierre Lemaitre, Susan M. Schrenner, Harumichi Ishigame, Brian D. Brown, James Dooley, Adrienne Liston, 18 June 2024, Immunity.
DOI: 10.1016/j.immuni.2024.05.023
The research was funded by the European Research Council and the Biotechnology and Biological Sciences Research Council.
