Three scientists—Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi—have been awarded the 2025 Nobel Prize in Physiology or Medicine for their transformative discoveries about how the immune system distinguishes friend from foe. The announcement, made on October 6, 2025, by the Karolinska Institute in Stockholm, marks a pivotal moment in the understanding of autoimmune diseases and the ongoing quest to harness the immune system for better health outcomes.
The trio’s work, which spans several decades and continents, uncovered the pathway known as peripheral immune tolerance. This mechanism is crucial in preventing the immune system from attacking the body’s own cells, a failure of which leads to autoimmune diseases such as Type 1 diabetes, rheumatoid arthritis, and lupus. As Marie Wahren-Herlenius, a rheumatology professor at the Karolinska Institute, explained to the Associated Press, the research “relates to how we keep our immune system under control so we can fight all imaginable microbes and still avoid autoimmune disease.”
The laureates come from diverse backgrounds but share a singular focus. Mary E. Brunkow, 64, is currently a senior program manager at the Institute for Systems Biology in Seattle. Fred Ramsdell, also 64, serves as a scientific adviser for Sonoma Biotherapeutics in San Francisco. Shimon Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan. Their combined efforts have not only deepened scientific understanding but have also laid the groundwork for new therapeutic approaches.
The journey to this Nobel recognition began in 1995, when Sakaguchi, driven by curiosity about why the immune system sometimes turns on itself, discovered a previously unknown subtype of T cells—regulatory T cells, or T-regs. These cells act as the immune system’s own security guards, tamping down overzealous immune responses that could otherwise harm the body. “I was curious about the mechanism of immune response that is supposed to protect oneself but also reacts to and attacks itself,” Sakaguchi recalled at a news conference in Osaka, as reported by CBC. His experiments in mice revealed that the thymus, long thought to be the sole training ground for immune cells, could not fully explain immune tolerance. The discovery of regulatory T cells opened a new chapter in immunology.
In 2001, working together at a biotech company, Brunkow and Ramsdell made another breakthrough. They identified a mutation in the Foxp3 gene as the culprit behind autoimmune disease in mice. “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. The significance of this finding quickly became apparent: the Foxp3 gene was a critical player in human health as well. Two years later, Sakaguchi linked the discoveries, demonstrating that Foxp3 controls the development of regulatory T cells, thereby curbing overreactive immune responses.
The impact of these discoveries, as noted by the prize-awarding body and reported by outlets such as Al Jazeera and CBC, has been profound. The research has “laid the foundation for a new field of research and spurred the development of new treatments, for example for cancer and autoimmune diseases.” Regulatory T cells have become a focal point in efforts to develop therapies that can either boost their numbers to treat autoimmune conditions or modulate their activity to enhance the body’s fight against cancer. More than 200 human clinical trials involving regulatory T cells are currently underway, with companies like Sonoma Biotherapeutics, Regeneron, Quell Therapeutics, AstraZeneca, and Bayer’s BlueRock exploring the therapeutic potential of these findings.
Despite the excitement, experts urge caution. Dr. Jonathan Schneck, a cellular immunology expert at Johns Hopkins University, told the Associated Press that while the discoveries have not yet led to new therapies, “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 as scientists build on their work.” The American Association of Immunologists echoed this sentiment, stating that the laureates’ research “has fundamentally reshaped our understanding of immune balance.”
For the winners themselves, the news came as a mix of disbelief and joy. Brunkow learned of her prize when she was woken by her dog barking at a news photographer on her front porch in Seattle. She had ignored an earlier call from the Nobel Committee, thinking it was spam. “When I told Mary she won, she said, ‘Don’t be ridiculous,’” her husband, Ross Colquhoun, shared with the Associated Press. Ramsdell, described by his colleague Jeff Bluestone as “one of the most humble people you’ll ever meet,” was reportedly away on a backpacking trip when the news broke. Sakaguchi, meanwhile, was interrupted during a press conference by a congratulatory call from Japanese Prime Minister Shigeru Ishiba. “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 prevention of diseases. That’s what our research is for,” Sakaguchi said, as quoted by the Associated Press.
The Nobel Prize in Physiology or Medicine is traditionally the first of the annual Nobel announcements, with prizes for physics, chemistry, literature, peace, and economics following in quick succession. The laureates will share prize money of 11 million Swedish kronor—nearly $1.2 million—along with gold medals, to be presented by the King of Sweden at a ceremony on December 10, the anniversary of Alfred Nobel’s death.
The significance of this year’s award goes beyond the scientific community. As Olle Kämpe, chair of the Nobel Committee, put it, “Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases.” The hope is that these foundational insights will continue to drive innovation, leading to breakthroughs that can transform lives for years to come.
With the Nobel spotlight shining on Brunkow, Ramsdell, and Sakaguchi, the world is reminded that curiosity, persistence, and collaboration remain at the heart of scientific progress—and that the immune system, with all its complexity, still holds secrets waiting to be unlocked.
