Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi have been awarded the Nobel Prize in Physiology or Medicine 2025 for their “groundbreaking discoveries concerning peripheral immune tolerance that prevents the immune system from harming the body,” the Nobel Committee announced on Monday.
The award recognizes decades of research that reshaped the understanding of the body’s immune defenses. “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.
The human immune system is designed to ward off thousands of different microbes daily. Yet many invading organisms have evolved to mimic human cells, raising the risk of the body’s defense mechanism mistakenly turning on its own tissues. The question of how the immune system determines what to attack and what to tolerate has long puzzled scientists. The laureates’ work provided the crucial answers.
Sakaguchi made the first breakthrough in 1995, challenging the prevailing belief that immune tolerance was established only through the elimination of potentially harmful cells in the thymus — a process known as central tolerance. “Sakaguchi showed that the immune system is more complex and discovered a previously unknown class of immune cells, which protect the body from autoimmune diseases,” the Nobel Committee said. His findings revealed the existence of regulatory T cells, which act as the immune system’s “security guards.”
In 2001, Brunkow and Ramsdell identified a key genetic factor underpinning immune regulation. Investigating why a particular strain of mice was prone to autoimmune diseases, they discovered mutations in a gene they named Foxp3. “They also showed that mutations in the human equivalent of this gene cause a serious autoimmune disease, IPEX,” the Nobel Committee noted.
Two years later, Sakaguchi linked these findings by proving that the Foxp3 gene governs the development of the regulatory T cells he had identified earlier. These cells are now recognized as central to preventing immune cells from turning against the body’s own tissues.
The discoveries by Brunkow, Ramsdell and Sakaguchi launched an entirely new field of immunology, known as peripheral tolerance. According to the Nobel Committee, this work has “spurred the development of medical treatments for cancer and autoimmune diseases,” while also holding promise for improving organ transplantation. Several therapies rooted in these discoveries are already in clinical trials.
By revealing how the immune system is kept in balance, the three scientists have illuminated one of the body’s most vital defense mechanisms, offering hope for transformative treatments in the years ahead.
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