The 2025 Nobel Prize Winners In Medicine

The 2025 Nobel Prize in Physiology or Medicine was awarded last 6 October to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for discovering how the immune system prevents itself from attacking the body.

The trio was recognized "for their discoveries concerning peripheral immune tolerance," a critical process that keeps the body’s defense system from turning on its own tissues.

Announced by the Nobel Assembly at the Karolinska Institute in Stockholm, the winners will share 11 million Swedish kronor (around £871,400). According to Prof Thomas Perlmann, secretary-general of the Nobel Assembly, only Sakaguchi could be reached at the time of the announcement.

"We have their phone numbers, but they’re probably on silent mode," he said.

Their work explains how immune cells, particularly T-cells, can distinguish between the body’s own tissues and harmful invaders. This discovery provides a foundation for understanding and treating autoimmune diseases such as type 1 diabetes and multiple sclerosis.

T-cells are white blood cells that detect and attack infected or cancerous cells. However, if these cells mistakenly target healthy tissues, the results can be devastating. By the late 1980s, scientists knew that harmful T-cells were eliminated in the thymus gland as they matured.

"Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases," mentioned Olle Kämpe, chair of the Nobel Committee.

Prof Marie Wahren-Herlenius of the Karolinska Institute added, "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 uncovered a second line of defense. He showed that mature T-cells carrying a protein called CD25 can suppress harmful T-cells. These special cells became known as regulatory T-cells, or T-regs.

"Essentially, they are the brakes of the immune system," explained Prof Adrian Liston from the University of Cambridge.

Brunkow and Ramsdell expanded on Sakaguchi’s findings by identifying a genetic link to immune regulation. They discovered that mice with a severe autoimmune disorder called scurfy had a mutation in the FoxP3 gene located on the X chromosome.

Later, they found that children with mutations in the same gene developed a rare autoimmune condition known as Ipex syndrome.

Sakaguchi later showed that FoxP3 controls the development of regulatory T-cells, confirming its essential role in maintaining immune balance.

"Regulatory T-cells keep most of us from having autoimmunity and allergy," Liston said. "By having a strong system of brakes, we are able to have stronger and faster immune reactions—the same way a car can have a better accelerator if it has good brakes."