STOCKHOLM / SEATTLE / OSAKA — Three scientists — Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi — have been awarded the 2025 Nobel Prize in Physiology or Medicine for their groundbreaking discoveries that explain how the immune system avoids attacking the body’s own tissues. Their research on peripheral immune tolerance has transformed the understanding of autoimmune diseases and opened new pathways for therapeutic innovation.
What They Discovered
Peripheral immune tolerance is the process that prevents immune cells from mistakenly attacking the body after they mature beyond the thymus. A central part of this system involves regulatory T cells, or T-regs, specialized cells that suppress harmful immune responses and maintain balance in the immune system.
In 1995, Shimon Sakaguchi identified a subset of T cells that acted as immune suppressors, suggesting that a specific mechanism kept the immune system in check. Building on that work, Mary Brunkow and Fred Ramsdell discovered in 2001 that mutations in a gene known as Foxp3 caused a severe autoimmune condition in mice known as “scurfy.” Later studies linked similar mutations in humans to a rare and often fatal autoimmune disorder called IPEX syndrome, found in young children.
Further research demonstrated that the Foxp3 gene was responsible for directing the development of regulatory T cells, confirming that this gene acts as a master controller for immune tolerance. Together, these discoveries explained how the immune system distinguishes between harmful invaders and the body’s own tissues — solving a decades-long mystery in immunology.
Global Reactions and Scientific Impact
At a press briefing in Osaka, Shimon Sakaguchi expressed deep gratitude, saying he never expected such recognition for what began as fundamental biological research. Mary Brunkow, speaking from her home in Seattle, described regulatory T cells as the immune system’s “braking system,” preventing it from “spinning out of control.”
The Nobel Assembly at the Karolinska Institute stated that the trio’s work has been “decisive for our understanding of how the immune system functions” and explained why most people do not develop autoimmune disease despite having highly reactive immune cells.
Their findings have already influenced more than 200 ongoing clinical trials worldwide focused on regulatory T-cell therapies. These therapies aim to treat autoimmune diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. Researchers are also exploring how to harness or inhibit regulatory T cells to improve cancer immunotherapies and organ transplantation outcomes.
One of the laureates, Fred Ramsdell, now serves as a scientific adviser at Sonoma Biotherapeutics, a California-based biotechnology company developing T-reg-based treatments for inflammatory diseases. Other biotech firms, including Quell Therapeutics and BlueRock, are pursuing similar research directions inspired by these discoveries.
Prize Details and Laureate Backgrounds
The 2025 Nobel Prize in Physiology or Medicine carries a monetary award of 11 million Swedish kronor, to be shared equally among the three laureates.
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Mary E. Brunkow is Senior Program Manager at the Institute for Systems Biology in Seattle, Washington.
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Fred Ramsdell, a veteran immunologist, serves as Scientific Adviser at Sonoma Biotherapeutics in San Francisco.
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Shimon Sakaguchi is Distinguished Professor at Osaka University in Japan and continues to lead immunological research focused on T-cell regulation.
Why It Matters
This Nobel Prize highlights one of the most important immunological advances of the past half-century — revealing how the immune system maintains tolerance to “self.” It provides the molecular and genetic foundation for understanding autoimmune disease and offers a blueprint for developing safer, targeted immunotherapies.
As the world faces rising cases of chronic inflammatory and autoimmune conditions, this discovery represents a turning point. It bridges fundamental biology with clinical innovation, ensuring that the body’s greatest defense system — the immune system — can protect without self-destruction.