The Nobel Assembly at Karolinska Institutet has awarded the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow of the Institute for Systems Biology in Seattle, Fred Ramsdell of Sonoma Biotherapeutics in San Francisco, and Shimon Sakaguchi of Osaka University in Japan for their discoveries concerning peripheral immune tolerance.
The award recognises a major advance in understanding how the immune system maintains balance and avoids attacking the body’s own tissues. Their work revealed how regulatory T cells prevent such self-destruction, transforming knowledge of autoimmune diseases and creating new paths for treatments in immunology and oncology.
“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” said Olle Kämpe, chair of the Nobel Committee.
Sakaguchi first uncovered the principle of peripheral immune tolerance in 1995, when he discovered a class of immune cells that protect the body from autoimmune attack. At that time, many believed immune tolerance arose only through central tolerance, a process eliminating harmful cells in the thymus. His research revealed a more complex mechanism of immune regulation.
In 2001, Brunkow and Ramsdell identified the gene that underpins this system. Their study of a mouse strain prone to autoimmune disease revealed a mutation in the Foxp3 gene. They later showed that similar mutations in humans cause a severe autoimmune condition known as IPEX. Two years later, Sakaguchi connected these findings, proving that Foxp3 controls the development of the cells he had first described. These cells, now called regulatory T cells, monitor immune activity and ensure that the system recognises the body as its own.
At a press conference in Stockholm on 6 October 2025, the Nobel Committee highlighted the clinical potential of these discoveries. Thomas Perlmann, the committee’s secretary, noted that more than 200 human trials involving regulatory T cells are under way, targeting conditions such as cancer and inflammatory bowel disease. While no therapies have yet reached market approval, the research has become a foundation for ongoing innovation.
Speaking from Osaka University, Sakaguchi described the honour as “tremendous,” according to Kyodo news agency. Brunkow reflected on the “collaborative nature of research” during a gathering at the Institute for Systems Biology on 7 October.
The laureates will share the prize amount of 11 million Swedish kronor. The medals will be presented by King Carl XVI Gustaf in Stockholm on 10 December 2025.
Mary E. Brunkow, born in 1961, earned her PhD from Princeton University and is Senior Program Manager at the Institute for Systems Biology. Fred Ramsdell, born in 1960, obtained his PhD in 1987 from the University of California, Los Angeles, and is Scientific Advisor at Sonoma Biotherapeutics. Shimon Sakaguchi, born in 1951, earned his MD in 1976 and PhD in 1983 from Kyoto University and is distinguished professor at the Immunology Frontier Research Center, Osaka University.
This year’s award also marks a milestone in Nobel history, as Brunkow becomes the 13th woman to receive the prize in Physiology or Medicine, following figures such as Gerty Cori in 1947 and Katalin Karikó in 2023.
The Physiological Society, Europe’s largest network of physiologists, praised the decision and called the discoveries a cornerstone in advancing immune tolerance research. In a statement, its president noted that the award aligns with current efforts to translate fundamental discoveries into clinical therapies for autoimmune disorders and transplantation medicine.
Autoimmune diseases affect millions worldwide, including conditions such as multiple sclerosis, rheumatoid arthritis and type 1 diabetes. Regulatory T cells, central to the laureates’ work, offer hope for therapies that modulate immune responses without broadly suppressing the system, which remains a limitation of existing drugs such as corticosteroids. In cancer treatment, similar mechanisms are being used to improve the precision of immunotherapies and to enhance organ transplant success by reducing the need for long-term immunosuppression.
The Nobel Foundation’s decision underscores the enduring role of immunology in shaping medical progress. Illustrations accompanying the announcement, created by Mattias Karlén and credited to “© The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén,” depict the key discoveries, including the Foxp3 gene, regulatory T cells, and their protective role in immune balance. Further scientific and popular summaries are available on the Nobel Prize website.
