Discovery of ‘new rules of the immune system’ could transform treatment of inflammatory diseases, say University of Cambridge scientists

A discovery about how our immune system operates that overturns our previous understanding could help lead to targeted treatments for everything from lengthy Covid infections to multiple sclerosis.

University of Cambridge scientists have discovered that a single large population of regulatory T cells - a type of white blood cell enabling us to heal - is moving around our bodies, rather than multiple specialist populations restricted to specific parts of the body.

These cells shut down inflammation and repair the collateral damage caused in cells after our immune system responds to injury or illness. Almost all diseases and injuries trigger the body’s immune system.

“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,” said Prof Adrian Liston, in Cambridge’s Department of Pathology, senior author of a paper in the journal Immunity. “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,”

Current anti-inflammatory drugs suppress the body’s whole immune system, rather than just the part needing treatment, which makes patients more vulnerable to infection.

But the findings suggest it could be possible to shut down the immune response in a specific part of the body, meaning higher and more targeted doses could be used, potentially speeding up results and reducing side effects.

Tests in mice of a drug developed by the researchers showed regulatory T cells can be attracted to specific body parts, boosted in number and activated to suppress immune response and rebuild one organ or tissue. Clinical trials in humans are now planned.

“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 Prof Liston.

The researchers analysed regulatory T cells in 48 different tissues in the bodies of mice to learn that the cells are not specialised or static, but move through the body to where they are needed.

“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,” said Prof Liston.

“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.

“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 of the symptoms we experience from infections such as Covid are not from the virus itself, but from the body’s immune system attacking the virus.

Most white blood cells attack infections in the body by triggering an immune response. But regulatory T cells shut down this immune response once it has done its job - and repair the tissue damage caused by it.

For some people, however, the process of shutting down the immune response is not very efficient, which can lead to ongoing problems.

The findings suggest a drug could be used to shut down the immune response in, for example, a patient’s lungs, while letting the immune system in the rest of the body continue to function normally.

The finding may also help those receiving organ transplants, who 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.

This makes them highly vulnerable to infections - but it could be possible to design new drugs to shut down the body’s immune response against only the transplanted organ in future.

The researchers are 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).