The 2025 Nobel Prize in Physiology or Medicine has been awarded to three scientists — Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi — for discoveries that revealed how the immune system avoids attacking the very body it’s designed to defend. Their work explained a crucial biological process known as peripheral immune tolerance and identified a new class of cells, called regulatory T cells, that keep the immune response under control.
Announced in Stockholm by the Nobel Assembly at the Karolinska Institute, this year’s prize recognizes decades of research that transformed understanding of immune regulation. The laureates’ findings uncovered how a precise system of checks and balances protects the body from autoimmune disorders while still enabling it to fight infection.
The immune system is often described as a defense network that distinguishes between invaders and self. Yet this process must be carefully managed; an overactive response can lead the body to attack its own tissues, resulting in autoimmune diseases. The Nobel laureates helped explain how the body prevents this internal conflict.
Shimon Sakaguchi, an immunologist from Japan, began exploring the question in the 1980s. While studying mice whose thymus glands had been removed, he noticed that their immune systems spiraled out of control, causing severe autoimmune reactions. His research led to the identification of a small subset of T cells that suppress excessive immune activity. In 1995, he defined these cells, later called regulatory T cells, as the immune system’s internal moderators, which were essential for maintaining balance.
Meanwhile, in the United States, scientists Mary E. Brunkow and Fred Ramsdell were investigating a mysterious strain of mice that suffered from an inherited immune disorder. Through painstaking genetic analysis, they pinpointed the cause: a defect in a gene on the X chromosome, which they named FOXP3. Further studies revealed that a similar mutation in humans leads to a rare condition known as IPEX syndrome, in which the immune system attacks multiple organs.
In 2003, Sakaguchi linked the discoveries, demonstrating that the FOXP3 gene governs the development of regulatory T cells. This finding revealed the molecular foundation of immune tolerance, or how the body distinguishes friend from foe.
The combined work of the three researchers has opened new frontiers in medicine. Their discoveries are guiding efforts to harness regulatory T cells for the treatment of autoimmune diseases, to reduce organ transplant rejection and to improve cancer immunotherapy by modulating immune responses.
Brunkow now works with the Institute for Systems Biology in Seattle, Ramsdell co-founded Sonoma Biotherapeutics in San Francisco and Sakaguchi conducts immunology research at Osaka University. Reflecting on the award, Sakaguchi said he hopes their work will continue to inspire progress toward new therapies.
The prize, which carries a monetary award of 11 million Swedish kronor (about $1 million), highlights how fundamental discoveries in biology can reshape modern medicine and deepen understanding of the body’s most complex defense system.
Sources: CNN, The Nobel Prize
