The Nobel Assembly at Karolinska Institutet has awarded the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their pioneering discoveries that unravel how the immune system avoids turning against the body it is meant to protect.
The trio is recognised “for their discoveries concerning peripheral immune tolerance,” a critical mechanism by which the immune system distinguishes self from non-self — preventing autoimmune disease by ensuring the body does not attack its own cells.
A Critical Breakthrough in Immunology
Every day, the human immune system is confronted by a vast array of potentially dangerous microbes. These invaders often resemble human cells in appearance, posing a formidable challenge: how to strike at the enemy without triggering friendly fire.
Brunkow, Ramsdell and Sakaguchi's research identified the immune system's internal safeguards — regulatory T cells — which act as sentinels, restraining other immune cells from targeting the body’s own tissues.
“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, in a statement.
Swimming Against Scientific Currents
In 1995, Shimon Sakaguchi, then working in Japan, made a landmark discovery that challenged prevailing immunological doctrine. At the time, scientists widely believed that immune self-tolerance was maintained solely through the elimination of rogue immune cells in the thymus — a mechanism known as central tolerance.
Sakaguchi demonstrated that a second line of defence existed outside the thymus. He identified a previously unknown subset of immune cells that actively suppress autoimmunity — a finding that would go on to redefine the field.
Six years later, Mary Brunkow and Fred Ramsdell, working independently in the United States, uncovered the genetic underpinning of this mechanism. Investigating a peculiar strain of mice prone to autoimmune disorders, they discovered a mutation in a gene they named Foxp3. Further studies revealed that mutations in the human version of this gene cause a rare but severe autoimmune disorder known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome).
By 2003, Sakaguchi had connected the dots. He demonstrated that Foxp3 is the key genetic driver of the regulatory T cells he had previously identified. These cells act as immune moderators, preventing the system from launching attacks on the body’s own organs and tissues.
The discoveries by the three laureates laid the foundation for the now-flourishing field of peripheral tolerance — a domain that continues to influence research into therapies for autoimmune diseases, cancer, and transplantation. Several treatments based on manipulating regulatory T cells are already in clinical trials.
This year’s award honours not only a deeper understanding of immunological harmony but also the profound medical implications of restoring or harnessing that balance.
Profiles of the Laureates
Mary E. Brunkow, born 1961, holds a Ph.D. from Princeton University. She is a Senior Program Manager at the Institute for Systems Biology in Seattle, USA.
Fred Ramsdell, born 1960, earned his Ph.D. from the University of California, Los Angeles. He is currently Scientific Advisor at Sonoma Biotherapeutics in San Francisco, USA.
Shimon Sakaguchi, born 1951, received his M.D. and Ph.D. from Kyoto University. He is Distinguished Professor at the Immunology Frontier Research Center, Osaka University, Japan.
The Nobel Prize in Physiology or Medicine comes with a monetary award of 11 million Swedish kronor, to be shared equally among the three recipients.
Source: nobelprize.org
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