A trio of scientists — two Americans and one Japanese — have been awarded the 2025 Nobel Prize in Physiology or Medicine for groundbreaking research that explains how the immune system prevents itself from attacking the body’s own tissues.
Their discoveries have led to new treatments for autoimmune diseases, cancer, and organ transplantation.
Pioneering Work on Peripheral Immune Tolerance
The prize was awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance — a biological safeguard that prevents the body’s defense mechanisms from turning on its own cells.
The Nobel Assembly said the trio’s work “launched the field of peripheral tolerance, spurring the development of medical treatments for cancer and autoimmune diseases.”
The winners will share the 11 million Swedish kronor ($1.2 million) prize. The Nobel Committee noted that the discoveries could also lead to more successful organ transplantations, with several related therapies currently undergoing clinical trials.
How the Body Keeps the Immune System in Check
Autoimmune diseases occur when T cells, which normally protect the body from viruses and bacteria, malfunction and attack healthy tissues instead. The immune system employs multiple strategies to prevent such errors.
One, called central tolerance, occurs in the thymus — a small organ in the chest — where defective T cells are destroyed before entering circulation.
However, not all malfunctioning T cells are eliminated. The Nobel-winning research uncovered how the body employs an additional safeguard known as peripheral tolerance, which neutralizes rogue immune cells that escape the thymus.
This discovery has provided critical insight into why some people develop autoimmune conditions while others remain healthy.
The Discovery That Changed Immunology
The journey began in 1995, when Shimon Sakaguchi, now a distinguished professor at Osaka University’s Immunology Frontier Research Center, identified a previously unknown class of immune cells that protected against autoimmune disease.
These cells would later become known as regulatory T cells, or Tregs, for their ability to suppress harmful immune reactions.
Six years later, in 2001, American researchers Mary Brunkow, now a senior program manager at Seattle’s Institute for Systems Biology, and Fred Ramsdell, a scientific adviser at Sonoma Biotherapeutics in San Francisco, discovered a genetic mutation that causes a severe autoimmune condition known as IPEX syndrome.
They traced the problem to a single gene — Foxp3 — which plays a critical role in regulating immune response.
In 2003, Sakaguchi’s lab confirmed that Foxp3 was the master gene governing the development of the same regulatory T cells he had discovered years earlier. This finding connected the genetic and cellular mechanisms of immune tolerance, forming the basis for a new understanding of immune regulation.
A Foundation for Modern Therapies
“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 findings have since inspired the creation of new immunotherapies aimed at restoring immune balance — treatments that could revolutionize care for diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis.
Beyond autoimmune disorders, the research has also influenced cancer immunotherapy, a field focused on reactivating the immune system to recognize and destroy tumor cells.
By better understanding how immune tolerance works, scientists can explore ways to temporarily lift these natural brakes when fighting cancer.
Reactions to the Announcement
At Monday’s announcement at Stockholm’s Karolinska Institute, Thomas Perlmann, secretary-general of the Nobel Committee, said he was only able to reach Sakaguchi by phone. “He was in his lab and sounded incredibly grateful,” Perlmann said.
“He said it was a fantastic honor and was quite taken by the news.” Perlmann added that Sakaguchi had left congratulatory voicemails for Brunkow and Ramsdell.
The award will be presented on December 10, the anniversary of Alfred Nobel’s death, as part of the traditional Nobel ceremony in Stockholm. Founded in 1901, the Nobel Prizes recognize outstanding contributions to humanity in science, literature, and peace.
This year’s prize in medicine opens the week of Nobel announcements, to be followed by awards in physics, chemistry, and literature later in the week.
