The Announcement
The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their pioneering discoveries that explain how the immune system learns to restrain itself — a process scientists call peripheral immune tolerance.
The trio’s work uncovered the biological mechanisms that stop the immune system from turning its weapons inward and attacking the body’s own cells — a failure of which lies behind autoimmune diseases such as diabetes, multiple sclerosis, and rheumatoid arthritis.
In announcing the prize at Stockholm’s Karolinska Institutet, the Nobel Committee praised the laureates for “revealing one of the most fundamental balancing acts of life — how immunity stays powerful yet peaceful.”
“These discoveries form the basis of a new era in immunology and medicine,” the committee said in its statement. “They have reshaped our understanding of self-tolerance and opened paths toward targeted treatments for autoimmune disease, transplantation, and cancer.”
The Science Behind the Discovery
The immune system’s mission is simple but perilous: it must attack dangerous invaders — viruses, bacteria, or cancerous cells — without harming the body’s own tissues. To achieve this, it develops a complex web of checks and balances.
For decades, scientists believed that immune tolerance — the body’s ability to distinguish between “self” and “foreign” — was determined early in life within the thymus, where self-reactive immune cells are deleted before they can cause harm.
But that explanation, known as central tolerance, turned out to be incomplete.
In the 1990s, Shimon Sakaguchi, a Japanese immunologist, discovered a mysterious subset of white blood cells that seemed to suppress excessive immune responses. He called them regulatory T cells, or Tregs — the body’s immune “brakes.”
Later, in 2001, Mary Brunkow and Fred Ramsdell, working independently at Immunex Corporation in the United States, identified a gene called Foxp3, mutations in which caused a fatal autoimmune disorder in mice. Around the same time, doctors found that mutations in the human version of this gene led to a rare but devastating condition known as IPEX syndrome, where the immune system destroys multiple organs in infants.
Their findings revealed that Foxp3 acts as a master switch — the genetic command center that gives Tregs their identity and suppressive power. Without it, the immune system cannot apply the brakes, and chaos ensues.
Together, Sakaguchi’s discovery of Tregs and Brunkow and Ramsdell’s genetic work on Foxp3 explained how the immune system maintains order in the body long after the thymus has done its job — a second, crucial layer of control known as peripheral immune tolerance.
Why It Matters
The implications of their work reach far beyond the lab bench.
1. A New Frontier in Treating Autoimmune Diseases
Autoimmune conditions — where the immune system attacks the body — affect hundreds of millions of people worldwide. Understanding how Tregs and Foxp3 function has inspired a wave of research into cell-based therapies designed to restore immune balance by boosting or engineering regulatory T cells.
Clinical trials are already underway for Treg therapies targeting type 1 diabetes, lupus, and multiple sclerosis, with early results showing promise in reducing inflammation without the harsh side effects of conventional immunosuppressive drugs.
2. Organ Transplantation Without Lifelong Drugs
Another tantalizing application lies in organ transplantation. Patients who receive donor organs must take lifelong immunosuppressants to prevent rejection, leaving them vulnerable to infection and cancer. Scientists hope that by harnessing regulatory T cells, doctors could one day induce true immune tolerance — allowing the body to accept a transplanted organ as its own.
3. Rethinking Cancer Immunotherapy
The same discovery also cuts both ways. In cancer, Tregs can act as protectors of the tumor, preventing the immune system from attacking malignant cells. By temporarily disabling these “brakes,” researchers are exploring ways to make immunotherapies more potent against cancer.
4. Balancing Immunity and Tolerance
The challenge, experts say, is to fine-tune the system — enhancing suppression where it’s excessive, and releasing the brakes where it’s too tight. “It’s a delicate dance,” said Dr. Lena Karlsson, an immunologist at Karolinska. “The immune system is like a high-performance car: you need both the accelerator and the brake to stay on the road.”
A Milestone in Modern Immunology
The Nobel recognition underscores how fundamental questions in biology — once purely theoretical — can lead to transformative medicine.
When Sakaguchi first proposed the existence of suppressive T cells three decades ago, the idea was controversial. Today, it forms the backbone of a new generation of precision immunotherapies.
Fred Ramsdell, now at Merck Research Laboratories, reflected in an interview that the discoveries were a reminder of the value of curiosity-driven science. “We weren’t trying to cure disease,” he said. “We were just trying to understand how the immune system keeps from destroying itself. The rest followed.”
Mary Brunkow, who began her work as a young scientist at Immunex, said she hoped the award would inspire more collaboration between basic researchers and clinicians. “The bridge between discovery and therapy is shorter than ever,” she said.
What’s next
The Nobel Prize in Medicine often signals not just a scientific triumph, but the dawn of a new therapeutic era. Just as discoveries in immunity led to vaccines, monoclonal antibodies, and checkpoint inhibitors, the insights from Brunkow, Ramsdell, and Sakaguchi could redefine how we treat diseases rooted in immune imbalance.
As the Nobel Committee concluded:
“Their discoveries have given medicine the tools to calm the storm — or unleash it when needed.”
In a century where both pandemics and autoimmune disorders threaten global health, understanding how to control the immune system without silencing it may prove to be one of the defining medical frontiers of our time.
For more visit: nobelprize.org/prizes/medicine
