On October 6, the Nobel Assembly at the Karolinska Institute awarded the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discoveries in how the immune system controls itself to avoid targeting the body. The three scientists were recognized for uncovering the crucial role of T-regs, the immune system’s own “brake mechanism,” and the gene that controls them, FOXP3, which together maintain the immune system’s delicate balance. This fundamentally changes the understanding of how the body maintains delicate balance.

“Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi have provided fundamental knowledge for how the immune system is regulated,” Dr. Marie Wahren-Herlenius, a member of the Nobel Committee, said. “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.”

Scientists before had thought that the immune system’s self-control depended almost entirely on what happens in the thymus, where a process called central tolerance occurs in which dangerous self-reactive immune cells are eliminated. But researchers have now discovered that this explanation didn’t tell the whole story.

According to NobelPrize.org, in 1995, Shimon Sakaguchi, then at Kyoto University, identified a special group of T cells marked by the molecule CD25. When he removed these cells from mice, their immune systems went haywire and attacked healthy tissue., The finding suggested that the body has a second layer of protection—cells that actively suppress harmful immune reactions after leaving the thymus.

A few years later, scientists Mary Brunkow and Fred Ramsdell traced a devastating mouse autoimmune disease called scurfy to a mutation in a previously unknown gene later named FOXP3. As reported by Reuters, they soon discovered that the same mutation in humans caused a fatal childhood disorder known as IPEX syndrome. The link between the gene and immune regulation was unmistakable.

Later studies confirmed that FOXP3 acts as a master switch—the defining gene that turns ordinary immune cells into T-regs. Without it, the immune system’s brakes fail completely. “Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” Olle Kämpe, chair of the Nobel Committee, said. 

The discovery of T-regs and FOXP3 reshaped nearly every area of immunology. Before their work, autoimmune disorders such as lupus, type 1 diabetes, and multiple sclerosis were largely viewed as mysterious misfires. Now, researchers can pinpoint when and how the immune system’s self-control mechanisms break down. 

Beyond autoimmunity, the discoveries have opened new frontiers in cancer, transplant medicine, and infectious disease, according to The Guardian. Tumors, for instance, can exploit T-regs to shield themselves from immune attack, which helps explain why some cancers resist immunotherapy. Conversely, boosting T-reg activity could help prevent the rejection of organ transplants.

Already, clinical trials are testing new therapies that expand or fine-tune T-regs to calm autoimmunity—or suppress them to unmask tumors in the immune system. The medical field is moving toward a future where doctors could adjust a patient’s immune balance as precisely as controlling a thermostat.

News outlets such as BusinessDay and JAPAN Forward called the trio’s work “a cornerstone of modern immunology.” Researchers say the next obstacle is turning these discoveries into powerful and precise therapies. Immune-modulating drugs must target only the right cells at the right time. Otherwise, the same system that protects us could also turn against us.

The laureates’ findings are also influencing the emerging field of tolerance engineering, where scientists are reprogramming immune cells to selectively ignore harmless targets like allergens or transplanted organs. It’s a vision of medicine where the immune system isn’t just fought—it’s taught.

This year’s Nobel Prize in Physiology or Medicine recognizes not just a discovery, but a transformation in how scientists view the immune system. What was once seen purely as a weapon of defense is now understood as a system of balance that requires both power and restraint. 

The next frontier of medicine may be built on that principle: learning not only how to fight disease, but how to restore equilibrium.