The 2025 Nobel Prize in Physiology or Medicine was announced on October 6, 2025, by the Nobel Assembly at Karolinska Institutet in Stockholm, Sweden. The prize was awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries on peripheral immune tolerance—the process that prevents the body’s immune system from attacking its own tissues.
Their research uncovered how the immune system maintains balance between defense and self-tolerance, a fundamental mechanism that protects against autoimmune diseases such as type 1 diabetes, multiple sclerosis, and lupus.
Sakaguchi, a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan, first identified a previously unknown class of immune cells—now known as regulatory T cells (Tregs)—in 1995. At the time, many scientists believed that immune tolerance occurred only through the elimination of self-reactive immune cells in the thymus, a process known as central tolerance. His discovery challenged this view, revealing that a second, peripheral layer of immune control exists outside the thymus to prevent self-destructive responses.
Brunkow, a senior program manager at the Institute for Systems Biology in Seattle, Washington, and Ramsdell, a scientific advisor at Sonoma Biotherapeutics in San Francisco, California, built upon this work in 2001 when they identified mutations in a gene they named Foxp3 in mice prone to autoimmune disease. They later showed that similar mutations in humans cause IPEX syndrome, a rare and severe autoimmune disorder. In 2003, Sakaguchi connected these discoveries by demonstrating that Foxp3 governs the development and function of regulatory T cells.
“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” says Olle Kämpe, chair of the Nobel Committee.
Beyond reshaping immunology, the laureates’ findings have laid the foundation for new therapies targeting autoimmune diseases, cancer, and transplant rejection. Treatments that harness or modulate regulatory T cells are currently being evaluated in clinical trials worldwide.
Brunkow, Ramsdell, and Sakaguchi will share the $1.17 million prize. Their work represents a milestone in modern medicine—revealing how the immune system’s “brakes” protect the body from itself and opening new frontiers for precision immunotherapy.
