The 2025 Nobel Prize in medicine reveals the immune system’s brakes
- Editorial Team SDG3
- Oct 14
- 3 min read
The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance, the subtle mechanisms that stop our immune system from attacking the body it is meant to protect. Their work unites decades of research into one clear answer, a special class of cells called regulatory T cells or Tregs, act as the body’s immune brakes, governed by the gene FOXP3.
This discovery reshaped modern immunology. It explained how healthy tissues are spared from immune destruction and why, when these mechanisms fail, autoimmune diseases such as type 1 diabetes or lupus arise. It also opened new possibilities for medicine, both to calm harmful immune reactions and, in some cases, to release them against cancer.
For most of the twentieth century, scientists believed that immune tolerance was achieved mainly during early development in the thymus, where self-reactive immune cells are deleted before they mature. Yet this theory could not explain why autoimmunity sometimes develops later in life, long after this “central tolerance” process has ended. Researchers began to suspect there was another layer of control, something that acted after immune cells had matured and spread throughout the body.
That missing layer was revealed in 1995, when Shimon Sakaguchi and his colleagues demonstrated that a small subset of T cells could suppress autoimmune reactions in mice. When these cells were removed, disease appeared, when restored, health returned. These were the elusive regulatory T cells. Six years later, Mary Brunkow and Fred Ramsdell identified the genetic key, a mutation in a gene they first called scurfin, later renamed FOXP3, caused fatal autoimmune disease in mice. Without this gene, the regulatory cells simply failed to form. Around the same time, they and others found that rare mutations in human FOXP3 led to a devastating disorder known as IPEX syndrome, offering direct proof of the gene’s importance.
By 2003, Sakaguchi’s group linked these threads together, showing that FOXP3 was the master switch that defines the Treg lineage. Together, the laureates built a unified picture of how the immune system polices itself, a system not based on destruction, but on restraint.
The Nobel Committee praised the laureates for filling a major conceptual gap in medicine. Their findings clarified the fine balance between immune attack and immune tolerance, and they provided a scientific foundation for new forms of therapy. Today, researchers are exploring how to use Tregs to treat autoimmune diseases or prevent organ rejection, while in cancer treatment the opposite strategy, reducing Treg activity, may help unleash the immune system against tumours. More than 200 clinical trials worldwide now draw on Treg and FOXP3 biology, according to reports on NobelPrize.org and Reuters.
Still, the path from discovery to treatment is delicate. Strengthening immune tolerance too much could leave patients defenceless against infections, while weakening it risks triggering new autoimmune attacks. The art of future therapy will be precision, adjusting the immune system gently rather than silencing it completely.
Each laureate’s career reflects a different side of this story. Mary Brunkow, trained at Princeton, now works at the Institute for Systems Biology in Seattle. Fred Ramsdell, who earned his doctorate at UCLA, has been instrumental in translating basic research into clinical work at Sonoma Biotherapeutics. Shimon Sakaguchi, a professor at Osaka University, has long been regarded as a pioneer of immunological self-regulation. Together, they share the Nobel’s 11 million Swedish kronor prize equally.
Their collective work is more than a scientific triumph, it is a reminder that understanding the body’s limits is as important as decoding its power. In an age of aggressive immune therapies and global health challenges, the principle of balance remains the core of sustainable medicine, echoing the vision behind Sustainable Development Goal 3 on health and wellbeing.
Explore the official Nobel Prize announcement and popular science background for more details, or follow coverage from The Guardian and AP News for broader perspectives on this milestone in human biology.
