The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their revolutionary work on peripheral immune tolerance — a discovery that has transformed the field of immunology. Their findings unveiled the crucial role of regulatory T cells (Tregs), the body’s internal guardians that prevent the immune system from turning against itself.
The announcement was made on October 6, 2025, by the Royal Swedish Academy of Sciences in Stockholm. The committee described their work as “decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases.”
Decoding the Body’s Defense Balance
The immune system’s primary role is to defend the body against harmful invaders like bacteria and viruses. But what stops it from attacking its own tissues? For decades, scientists believed that self-tolerance — the ability to distinguish self from non-self — occurred solely through a process known as central tolerance, which develops in the thymus.
However, in 1995, Japanese immunologist Shimon Sakaguchi discovered something that challenged that belief. He identified a previously unknown class of immune cells that acted as regulators — controlling immune responses and maintaining balance. These regulatory T cells became the foundation for understanding how the immune system avoids self-destruction.
A Genetic Key to Autoimmune Diseases
Several years later, in 2011, American researchers Mary E. Brunkow and Fred Ramsdell uncovered another piece of the puzzle. While studying a specific mouse strain prone to autoimmune disorders, they found mutations in a gene they named Foxp3. Their research revealed that this gene played a vital role in immune regulation.
More significantly, they demonstrated that mutations in the human equivalent of Foxp3 lead to a rare but severe autoimmune disorder known as IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome.
Connecting the Dots: Sakaguchi’s Breakthrough
In 2003, Sakaguchi linked these discoveries together and proved that the Foxp3 gene governs the development of the same regulatory T cells he had identified years earlier. These cells act as the immune system’s peacekeepers — ensuring that the body’s defense mechanisms tolerate its own tissues, preventing self-inflicted damage.
This understanding reshaped how researchers view autoimmune diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The discovery not only provided answers to long-standing questions about immune regulation but also opened pathways for potential therapeutic interventions in autoimmune disorders and transplantation medicine.
The Laureates and Their Contributions
- Mary E. Brunkow holds a PhD from Princeton University and currently serves as Senior Program Manager at the Institute for Systems Biology, Seattle.
- Fred Ramsdell is Scientific Advisor at Sonoma Biotherapeutics, USA, focusing on immune modulation therapies.
- Shimon Sakaguchi, a Distinguished Professor at the Immunology Frontier Research Center, Osaka University, continues to be a leading figure in global immunology research.
Their collective work represents decades of perseverance and has provided a deeper understanding of how the immune system maintains balance — a cornerstone of modern medical science.
A Tradition of Recognizing Human Advancement
The Nobel Prize in Physiology or Medicine traditionally opens the annual Nobel week. This year’s announcement follows the 2024 award to Victor Ambros and Gary Ruvkun for their discovery of microRNA and its role in gene regulation.
The 2025 award ceremony will be held on December 10, the anniversary of Alfred Nobel’s death, with each laureate receiving 11 million Swedish kronor (about $1.2 million), a gold medal, and a diploma.
The Legacy of Alfred Nobel
The Nobel Prizes were established by Swedish inventor Alfred Nobel, who dedicated his estate to honoring individuals and organizations that “confer the greatest benefit to humankind.” His vision continues to recognize scientific achievements that advance knowledge and improve human life — and this year’s Medicine laureates truly embody that legacy.
