The Nobel prize in physiology or medicine 2025 has been awarded to three scientists for their work on how the immune system is prevented from attacking the body.
Mary E Brunkow, now at the Institute for Systems Biology in
Seattle, Fred Ramsdell, now at Sonoma Biotherapeutics in
San Francisco, and Shimon Sakaguchi, now at Osaka University in Japan, have been awarded the prize “for their discoveries concerning peripheral immune tolerance”.
Announced on Monday by the Nobel assembly at the Karolinska Institute in Stockholm, Sweden, the winners will share a prize of 11m Swedish kronor (about £871,400).
At the time of the announcement, Prof Thomas Perlmann, a member of the Karolinska Institute’s Nobel committee, revealed he had managed to reach only Sakaguchi.
“We have their phone numbers, but they’re probably on silent mode,” he said.
The award celebrates a fundamental discovery relating to T-cells, an important player in the immune system. T-cells are a type of white blood cell, produced in the bone marrow, that help to flag invading microbes and kill infected or cancerous cells.
It is crucial that T-cells do not attack the body’s healthy tissues, as this can cause autoimmune diseases such as type 1 diabetes and multiple sclerosis.
By the late 1980s it was known that harmful T-cells are eliminated in an organ called the thymus gland, where developing T-cells migrate to mature.
Prof Marie Wahren-Herlenius, of the Karolinska Institute, said: “For a long time, this was believed to be the only way self-tolerance is obtained. However, some self reactive cells escape out into our circulation and are potentially dangerous.”
Sakaguchi revealed a second mechanism by which self-tolerance arises, showing harmful T-cells can be eliminated by mature T-cells that carry a protein on their surface called CD25. These cells became known as regulatory T-cells.
Prof Adrian Liston, from the University of Cambridge, said: “Essentially, they are the breaks of the immune system”.
Brunkow and Ramsdell added another piece to the puzzle, revealing mice with a severe autoimmune disorder called scurfy have a mutation in their X chromosome within a gene the pair called FoxP3. They then showed that children with mutations in this gene develop a rare autoimmune condition called Ipex syndrome.
Sakaguchibecame the first to show the FoxP3 gene controls the development of regulatory T-cells, revealing its importance for the emergence of self-tolerance.
Liston said: “Regulatory T-cells keep most of us from having autoimmunity and allergy. And another part is that by having a strong system of breaks present we are able to have stronger and faster immune reactions – the same way that a car can have a better accelerator if it has good breaks. It really is an essential part of the immune system, and leads to early fatal disease in childhood if it is broken.”
Wahren-Herlenius said the discoveries have spurred on the development of several potential treatments.
“Clinical trials are ongoing to increase the number of regulatory T-cells for suppressing unwanted immune reactions in autoimmune disease or following organ transplantation,” she said, adding that the opposite approach was used in trials for cancer.
“Cancer cells can make use of our regulatory T-cells to avoid immune reactions that could destroy the cancer cells,” she said. “For cancer treatments, the focus is therefore on down regulating or destroying the regulatory T-cells so that our immune system can act against the malignant cells.”
Prof Danny Altmann, an immunologist at Imperial College London,
said: “A huge part of the advance over the past 30 years in understanding the immune system has come with the description, definition and characterisation of the regulatory T-cells in diverse aspect of health and disease.
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Prof Adrian Hayday, of King’s College London and the Francis Crick Institute, said the prize for the discovery of regulatory T-cells – or T-reg cells – was long-expected, although there was further work to do to fully harness the discoveries.
“There really is an enormous amount that we still don’t know about T-reg cells, and the capacity to routinely exploit T-reg cells and their properties in the clinic has not yet been realised,” he said. “However, I’m quite confident it will be.”
