The 2025 Nobel Prize in Physiology or Medicine was awarded to American researchers Mary Brunkow of the Institute for Systems Biology in Seattle, Fred Ramsdell of Sonoma Biotherapeutics in San Francisco, and Japanese scientist Shimon Sakaguchi of Osaka University. They were honored for discovering peripheral immune tolerance, a mechanism that protects the body from attacking its own tissues and from developing autoimmune diseases.
According to the Nobel Committee, the laureates’ decades-long work laid the foundation for a new field in immunology and helped spur the development of treatments for cancer and autoimmune disorders. The immune system identifies viruses, bacteria and cancer cells through T cells formed in the thymus, but it also needs a mechanism that restrains mistaken attacks on the body itself.
When that system fails, immunity may begin treating the body’s own tissues as foreign. This is linked, among other conditions, to multiple sclerosis, type 1 diabetes and rheumatoid arthritis. In cancer, the opposite failure can occur: the immune system does not recognize tumor cells as a threat and allows them to keep multiplying.
For a long time, scientists believed tolerance was formed only in the central organs of the immune system, where potentially dangerous cells are filtered out during maturation. But in the 1980s, while studying the thymus, Sakaguchi concluded that the body has an additional protective mechanism. In 1995, he described a new class of regulatory T cells that do not attack foreign agents but instead suppress the activity of other immune cells outside the central immune organs.
At the same time, Brunkow and Ramsdell were investigating the causes of severe autoimmune disease in mice after radiation exposure and identified a defect in the FOXP3 gene. It was later established that this gene is also present in humans and is linked to the rare autoimmune IPEX syndrome. Sakaguchi subsequently became the first to show that FOXP3 is required for the formation of regulatory T cells.
“This discovery changed our view of many diseases and continues to do so,” said Anne Pesenacker, an immunologist at University College London.
Current research shows that in autoimmune diseases there are either too few regulatory T cells or they do not function properly. In cancer, by contrast, there may be too many of them, which suppresses the immune response that is actually needed. Researchers therefore see regulatory T cells and FOXP3 as promising therapeutic targets for more precise control of the immune system.