October 08, 2025
3 min read
The 2025 Nobel Prize in Physiology or Medicine has been awarded to a trio of researchers whose work identified and shed light on regulatory T cells and how they prevent the immune system from attacking the body.
Mary E. Brunkow, PhD, of the Institute for Systems Biology, in Seattle, Fred Ramsdell, PhD, of Sonoma Biotherapeutics, in San Francisco, and Shimon Sakaguchi, MD, PhD, of Osaka University’s Immunology Frontier Research Center, in Japan, will share the honor — and the 11 million Swedish kronor prize — for their “fundamental discoveries relating to peripheral immune tolerance,” according to a statement from the Nobel Committee.
“This year’s Nobel Prize in Physiology or Medicine relates to how we keep our immune system under control so we can fight all imaginable microbes and still avoid autoimmune disease,” Marie Wahren-Herlenius, MD, PhD, a rheumatologist at the Karolinska Institute in Stockholm, and member of the Nobel Committee, said at the press conference announcing the prize.
“Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have provided fundamental knowledge of how the immune system is regulated,” she added.
Wahren-Herlenius additionally noted how their discoveries have triggered the development of several potential new treatments for autoimmune disease and cancer.
“Clinical trials are ongoing to increase the number of regulatory T cells for suppressing unwanted immune reactions in autoimmune disease, or following organ transplantation,” she said. “This is done either by injecting growth factors that stimulate regulatory T cells, or by multiplying regulatory T cells in laboratories, which can then be given to patients. The opposite approach is used in trials for cancer, where the focus is on down-regulating or destroying the regulatory T cells so that our immune system can act against the malignant cells.”
Georg Schett, MD, who has recently made headlines in his own right as a pioneer of chimeric antigen receptor T-cell therapy in autoimmune disease at the Friedrich-Alexander University of Erlangen-Nuremberg, in Germany, said the use of regulatory T cells (or Tregs) for diseases like lupus and systemic sclerosis has become critical in the wake of the Nobel laureates’ discoveries.
“Using Tregs as therapeutic tool to stop inflammation in severe forms of rheumatic diseases becomes increasingly important,” Schett told Healio. “Such approaches may either use polyclonal Treg infusions or engineered Tregs, such as CAR-Treg, which bind via the CAR to target cells — for example, B cells — get activated and then exert its regulatory capacity at sites of inflammation without killing any cell.”
Discoveries ‘unleashed a whole new field’
The initial breakthrough came in 1995, when Sakaguchi and colleagues discovered a previously unknown class of immune cells — dubbed regulatory T cells — that protect the body from autoimmune diseases. The team demonstrated that mice with depleted regulatory T cells developed autoimmune disease, and that injecting regulatory T cells provided protection against disease progression.
Prior to the groundbreaking work, many researchers believed that immune tolerance developed solely due to potentially harmful immune cells being eliminated in the thymus via a process called central tolerance, according to the Nobel Committee.
“Many researchers were skeptical about the existence of regulatory T cells,” said Wahren-Herlenius.
Later in 2001, Brunkow and Ramsdell presented data explaining why a specific mouse strain was particularly vulnerable to autoimmune diseases. Their team had discovered these mice harbored a mutation in a gene they named Foxp3. They additionally revealed that mutations in the human equivalent of this gene cause the rare autoimmune disease IPEX.
“Today, it’s possible to map a whole mouse genome in a few days, but at the time it was an incredible challenge and like looking for a needle in a haystack,” said Wahren-Herlenius.
Sakaguchi in 2003 then married these discoveries together when he demonstrated that the Foxp3 gene controls the development of regulatory T cells, which monitor other immune cells and prevent the immune system from harming the body’s own tissues.
“This was soon followed by reports by other scientists, and unleashed a whole new field in immunology,” said Wahren-Herlenius. “Subsequent studies show that when all three active T cells get activated, the regulatory T cells act to control them, both through cell-cell contacts and by soluble molecules. In this way, immune tolerance can be maintained without deleting too many T cells, which could be needed for our protection against current or future microbes.”
According to Schett, regulatory T cells are crucial to understanding autoimmune disease.
“Mutations of the essential transcription factor for Treg (foxp3) lead to severe inflammation and autoimmunity, with death within the first year of age — in cases like IPEX syndrome — if not treated,” Schett told Healio.
“Also, in many autoimmune diseases, dysfunctionality of Treg has been documented suggesting that their low performance fosters autoimmune diseases such as in rheumatoid arthritis and systemic lupus erythematosus,” he added. “All these data suggest that Tregs are powerful regulators of the immune system, with their physiological role in preventing exaggerated inflammation and controlling autoimmunity.”
For more information:
Georg Schett, MD, can be reached at georg.schett@uk-erlangen.de.
