STOCKHOLM — The 2025 Nobel Prize in Physiology or Medicine was awarded on Monday to Mary E. Brunkow, Fred Ramsdell, and Dr. Shimon Sakaguchi for their groundbreaking discoveries that explain how the immune system distinguishes harmful invaders from the body’s own cells.
Their independent yet complementary research revealed a key mechanism known as peripheral immune tolerance, which prevents the immune system from attacking the body’s own tissues. The discovery has advanced understanding of autoimmune diseases such as Type 1 diabetes, rheumatoid arthritis, and lupus, and has opened new possibilities for improving organ transplants and cancer 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.
Brunkow, 64, is currently a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, also 64, serves as a scientific adviser for Sonoma Biotherapeutics in San Francisco. Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan.
The Nobel Assembly at the Karolinska Institute in Stockholm announced the prize, the first of the 2025 Nobel awards. The physics prize will follow on Tuesday, chemistry on Wednesday, literature on Thursday, and the Nobel Peace Prize on Friday. The Nobel Memorial Prize in Economics will be announced on October 13.
Sakaguchi’s experiments in mice during the 1990s revealed that immune regulation involved more than the thymus pathway previously known to eliminate rogue immune cells. In 1995, he identified a new type of T cell, now known as regulatory T cells, or T-regs, which suppress overactive immune responses.
In 2001, Brunkow and Ramsdell discovered that a mutation in the Foxp3 gene was responsible for autoimmune disorders in mice, linking the gene to immune system regulation. Two years later, Sakaguchi demonstrated that Foxp3 controls the development of regulatory T cells, establishing the connection between the gene and immune tolerance.
“From a DNA level, it was a really small alteration that caused this massive change to how the immune system works,” Brunkow told the Associated Press.
Back in Japan, Sakaguchi noted that “it was getting a lot of attention as one gene that can explain multiple autoimmune diseases, but still, why the gene causes the diseases was a mystery.”
Experts have hailed the trio’s work as foundational. “The winners’ work has fundamentally reshaped our understanding of immune balance,” said the American Association of Immunologists.
Dr. Jonathan Schneck of Johns Hopkins University added that while the discoveries have yet to yield new therapies, they are paving the way for future breakthroughs. “It’s incredibly important to emphasize, this work started back in 1995, and we’re reaping the benefits but yet have many more benefits we can reap,” he said.
At a press conference following the announcement, Sakaguchi described his award as “a happy surprise.” He added, “There are many illnesses that need further research and treatment, and I hope there will be further progress in those areas so that findings will lead to the prevention of diseases. That’s what our research is for.”
Brunkow said she initially ignored a call from the Nobel Committee, assuming it was spam. “My phone rang and I saw a number from Sweden and thought: ‘That’s just, that’s spam of some sort,’” she recounted with a laugh.
Ramsdell, known for his humility, had not yet been reached as of the announcement. “It’s going to be great for us to toot his horn for him,” said Jeff Bluestone, CEO of Sonoma Biotherapeutics.
The three laureates will share a prize of 11 million Swedish kronor (nearly $1.2 million). The official award ceremony will be held on December 10, the anniversary of Alfred Nobel’s death.
