The 2025 Nobel Prize in Physiology or Medicine has been awarded to three scientists—Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi—for their groundbreaking discoveries concerning “peripheral immune tolerance,” a mechanism that prevents the immune system from attacking the body’s own tissues.
The Nobel Assembly at Karolinska Institutet today announced that the prize recognizes the laureates for identifying the immune system’s “security guards,” known as regulatory T cells, which are crucial for keeping the body’s powerful defense system in check.
Mary E. Brunkow of the Institute for Systems Biology in Seattle, USA; Fred Ramsdell of Sonoma Biotherapeutics in San Francisco, USA; and Shimon Sakaguchi of Osaka University in Osaka, Japan, share the prestigious award.
“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 body’s immune system is constantly vigilant, protecting against thousands of microbes. However, its immense power necessitates strict regulation to avoid attacking healthy organs—a condition known as autoimmune disease.
The Discovery of the Immune System’s “Check”
The seeds of the discovery were sown in 1995 when Shimon Sakaguchi challenged the prevailing scientific belief that immune tolerance was solely established in the thymus (central tolerance). Sakaguchi swam against the tide to identify a previously unknown class of immune cells that specifically protected the body from autoimmune disorders.
The second key piece of the puzzle came in 2001 from Mary E. Brunkow and Fred Ramsdell. They provided the genetic explanation for a mouse strain’s particular vulnerability to autoimmune diseases: a mutation in a gene they named Foxp3. They further showed that mutations in the human equivalent of Foxp3 cause a severe autoimmune condition known as IPEX.
Two years later, Sakaguchi was able to link the findings, proving that the Foxp3 gene governs the development of the very cells he had identified in 1995. These are the regulatory T cells, which actively monitor other immune cells and ensure tolerance for the body’s own tissues.
The collective work of the laureates has fundamentally launched the field of peripheral tolerance. It has already spurred the development of new medical treatments, many of which are currently in clinical trials, for a range of conditions including cancer and autoimmune diseases. The research is also anticipated to lead to more successful organ transplantations.
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