STOCKHOLM — The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for uncovering how the immune system stops itself from attacking the body’s own cells — a process called peripheral immune tolerance.
The Nobel Assembly at the Karolinska Institutet in Sweden said the three scientists’ discoveries revealed how certain immune cells, known as regulatory T cells, act as the body’s “peacekeepers.” These cells make sure the immune system stays balanced, preventing harmful reactions that can cause autoimmune diseases.
The immune system protects us from thousands of bacteria and viruses every day. But that power comes with risk: if it makes a mistake, it can destroy healthy tissue. Normally, young immune cells that could harm the body are removed early in their development in an organ called the thymus.
However, the laureates showed that this “central tolerance” is not enough. In the rest of the body — the periphery — another system of control is needed. That is where regulatory T cells come in. They monitor other immune cells and stop them from turning against the body.
In 1995, Shimon Sakaguchi discovered a new type of immune cell that prevented autoimmune diseases. His findings challenged the long-held belief that immune tolerance could only happen in the thymus.
A few years later, in 2001, Mary Brunkow and Fred Ramsdell identified a gene, called Foxp3, that was critical to immune balance. They found that when Foxp3 was damaged in mice, the animals developed severe autoimmune diseases. Mutations in the human version of that gene cause a rare but dangerous immune disorder known as IPEX syndrome.
By 2003, Sakaguchi connected these findings, showing that the Foxp3 gene controls the development of the regulatory T cells he had discovered earlier. Together, their work revealed how the immune system learns to recognize and tolerate the body’s own tissues while still defending against infections.
Their discoveries opened an entirely new field of study, leading to potential treatments for diseases like type 1 diabetes, multiple sclerosis, and lupus — conditions where the immune system turns against the body. Researchers are also exploring how to adjust regulatory T cells to improve cancer therapies and make organ transplants safer by reducing rejection.
Olle Kämpe, chair of the Nobel Committee, said the findings were “decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases.”
The three scientists will share an award of 11 million Swedish kronor, about $1 million.
Brunkow, born in 1961, is a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, born in 1960, serves as a scientific adviser at Sonoma Biotherapeutics in San Francisco. Sakaguchi, born in 1951, is a distinguished professor at Osaka University.
