In a landmark announcement on October 6–7, 2025, the Nobel Assembly at the Karolinska Institute awarded the 2025 Nobel Prize in Physiology or Medicine to three pioneering scientists: Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi. The trio was recognized for their groundbreaking discoveries that revealed how the immune system prevents itself from attacking the body’s own healthy tissues—a fundamental process known as peripheral immune tolerance. Their collective work transformed the understanding of immunology and opened up new frontiers in treating autoimmune diseases, improving organ transplant outcomes, and refining cancer immunotherapy.
The research that earned this year’s laureates global acclaim centers on a specialized group of immune cells called regulatory T cells, or Tregs. These cells function as the immune system’s peacekeepers, preventing it from turning its powerful defenses against the body itself. Under normal circumstances, the immune system is finely tuned to detect and eliminate pathogens such as viruses and bacteria. But if this balance fails, the body can mistakenly attack its own tissues, leading to chronic inflammatory and autoimmune diseases. The discovery of Tregs and the gene that controls them, known as FOXP3, fundamentally reshaped scientists’ understanding of this delicate equilibrium.
The scientific journey leading to this recognition began decades ago. In the early 1990s, Japanese immunologist Shimon Sakaguchi proposed the existence of a subset of T cells that suppressed immune responses, thereby maintaining tolerance to self-antigens. His experiments demonstrated that when these suppressor cells were removed, mice developed severe autoimmune conditions. This observation provided the first tangible evidence that the immune system had its own internal braking mechanism to prevent self-destruction. However, the molecular identity and regulatory basis of these cells remained unknown until the work of Brunkow and Ramsdell.
Mary E. Brunkow and Fred Ramsdell, working independently in the United States, helped uncover the genetic key that underlies this immune tolerance. Their investigations led to the discovery of the FOXP3 gene, a transcription factor that serves as the master regulator of Treg development and function. Through genetic studies in animal models, Brunkow and Ramsdell observed that mutations in FOXP3 resulted in a fatal autoimmune syndrome, in which the immune system turned destructively against the body. The identification of this gene not only confirmed the existence of regulatory T cells but also established how they function at the molecular level. This discovery became one of the defining moments in modern immunology, influencing everything from basic research to clinical medicine.
The implications of their work have been profound. In autoimmune diseases such as multiple sclerosis, type 1 diabetes, and lupus, the immune system’s failure to recognize self-tissues results in relentless inflammation and damage. By understanding how regulatory T cells function, scientists have gained critical insights into how these diseases might be controlled by restoring immune balance. Researchers are now developing therapies that harness or expand a patient’s own Tregs to suppress unwanted immune responses, potentially offering treatments that address the root causes of these diseases rather than just managing symptoms.
The discovery has also found relevance in organ transplantation, a field long challenged by the problem of immune rejection. The possibility of using regulatory T cells to promote long-term tolerance of transplanted organs without the need for lifelong immune-suppressing drugs is being actively investigated. Clinical trials are already exploring Treg-based cellular therapies that could allow transplant recipients to maintain organ function with fewer side effects and better overall outcomes.
Conversely, in the realm of cancer immunotherapy, the challenge lies not in suppressing immune activity but in amplifying it. Because tumors often exploit regulatory T cells to avoid immune detection, scientists are exploring strategies to temporarily disable or inhibit Tregs in the tumor environment. This could enable the immune system to more effectively recognize and destroy cancer cells. Thus, the same discovery that offered hope for controlling autoimmune diseases has also provided vital insights into how the immune system might be reawakened to fight cancer more effectively.
When the Nobel Prize announcement was made, it briefly became a story of both science and serendipity. Fred Ramsdell was reportedly unreachable for several hours because he was on a digital-detox hiking trip somewhere in the western United States, unaware that he had just been awarded one of the world’s highest scientific honors. Once he received the news, colleagues described his reaction as humble and reflective of the collaborative spirit that has long defined his career. Mary E. Brunkow, whose early genetic research laid the foundation for the discovery of FOXP3, emphasized that their work was a product of persistence and cross-disciplinary cooperation. She noted that the discovery represents “a fusion of molecular biology, genetics, and immunology coming together to solve one of medicine’s deepest mysteries.”
Shimon Sakaguchi, who first conceptualized the role of suppressor T cells decades earlier, expressed gratitude for the recognition and highlighted the broader significance of immune regulation. In comments shared by the Karolinska Institute, he said that the immune system functions much like a society—it must have checks and balances to prevent chaos. His analogy captures the essence of their achievement: understanding how the immune system’s “rules and regulators” maintain harmony within the body.
The Nobel Committee praised the laureates for transforming a fundamental concept in biology into one with far-reaching clinical potential. Their discoveries have already led to experimental therapies that are reshaping how diseases of the immune system are treated. Experts predict that the coming decade will see rapid advances in immune engineering, leveraging the principles discovered by Brunkow, Ramsdell, and Sakaguchi. New technologies such as CRISPR gene editing and cell-based therapies are expected to refine the ability to control immune tolerance with unprecedented precision.
As the scientific community reflects on this year’s Nobel announcement, it is clear that the work of these three scientists has not only solved a long-standing biological mystery but also opened an entirely new chapter in medicine. By revealing how the immune system prevents itself from attacking the body, Brunkow, Ramsdell, and Sakaguchi have illuminated one of life’s most essential balancing acts. Their discovery continues to influence the treatment of autoimmune diseases, transplant rejection, and cancer—fields where the battle between immune defense and self-tolerance defines the boundary between health and disease.