2025 Nobel Prize in Medicine to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their "discoveries concerning peripheral immune tolerance."

American scientists Mary E. Brunkow and Fred Ramsdell and Japanese scientist Shimon Sakaguchi won the Nobel Prize in Medicine on Monday for their research on how the body controls the immune system.

The three were honored for their "discoveries concerning peripheral immune tolerance," the Nobel committee announced in a statement.

"This year's Nobel Prize in Physiology or Medicine is about how we control our immune system so that it can fight off every conceivable microbe without causing autoimmune diseases," explained Marie Wahren-Herlenius, a professor at the Karolinska Institutet.

Mary E. Brunkow of the Systems Biology Institute in Seattle, Washington, Fred Ramsdell of Sonoma Biotherapeutics, Washington, and Shimon Sakaguchi of Osaka University, Japan, are receiving the award for their discoveries concerning peripheral immune tolerance, the mechanism that prevents our powerful immune system from attacking our own body. “This is fundamental work in our understanding of how the immune system regulates itself,” said Marie Wahren-Herlenius,

The immune system protects us every day from viruses, bacteria, and other microbes. Without it, we couldn't live. But if it overworks, it can attack our own bodies and cause diseases, such as autoimmune diseases.

The three laureates have discovered how the immune system stays under control, identifying regulatory T cells, the " security guards " that prevent our defenses from destroying our own tissues. Their findings laid the foundation for a new field of research and have spurred the development of new treatments for cancer, autoimmune diseases, and transplant rejection, some of which are already being evaluated in clinical trials.

"Their discoveries have been crucial to understanding how the immune system works and why not all of us develop serious autoimmune diseases," said Olle Kämpe, chairman of the Nobel Committee.

For decades, researchers believed that immune tolerance was due solely to a “central selection” process in the thymus, where T cells that react against the body’s own cells are eliminated.

But in 1995 , Shimon Sakaguchi challenged that view by showing that the immune system is more complex: he discovered a new type of T lymphocyte, the regulatory T cells, which act outside the thymus and maintain immune balance through peripheral control.

Their work showed that, in addition to central mechanisms, there is a " surveillance " system that calms the rest of the immune cells, preventing uncontrolled responses that can damage organs and tissues.

The second key piece of discovery came in 2001, when Mary E. Brunkow and Fred Ramsdell identified the Foxp3 gene , responsible for a serious autoimmune disease in a strain of mice known as scurfy.

By studying the gene in humans, they showed that mutations in FOXP3 cause IPEX syndrome, a rare and fatal disease that affects young children.

Two years later, Sakaguchi combined both lines of research: he demonstrated that Foxp3 controls the development of regulatory T cells, thus confirming its essential role in peripheral immune tolerance.

The discoveries of the three laureates have transformed modern immunology. They have paved the way for new therapies that precisely modulate the immune system:

In cancer, scientists seek to disable regulatory T cells that protect tumors from immune attack.

In autoimmune diseases, these cells are increased or activated to stop the attack of the immune system.

In transplants and cell therapies, treatments based on the expansion or modification of the patient's own regulatory T cells are being developed to prevent organ rejection.

Today, three decades after those pioneering observations, the discoveries of Brunkow, Ramsdell, and Sakaguchi constitute a cornerstone of modern medicine. They have revealed how the immune system self-regulates, how it prevents disruption to our defenses, and how these mechanisms can be harnessed to heal.

With their work, the three scientists have provided fundamental knowledge about how the immune system is kept in check, a discovery that, in the words of the Nobel Committee, “ has conferred the greatest benefit on humanity .” “Their findings have laid the foundation for a new field of research and have spurred the development of new treatments, for example for cancer and autoimmune diseases,” the jury explained.