On Oct. 6, 2026, The Nobel Assembly has awarded the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

The body’s powerful immune system must be regulated, or it may attack our own organs. Mary E. Brunkow, Senior Program Manager, Institute for Systems Biology, Seattle, WA; Fred Ramsdell, Scientific Advisor, Sonoma Biotherapeutics, San Fransisco, CA; and Shimon Sakaguchi, Distinguished Professor at the Immunology Frontier Research Center, Osaka University, Osaka, Japan, made groundbreaking discoveries concerning peripheral immune tolerance that prevents the immune system from harming the body. Their discoveries have laid the foundation for a new field of research and spurred the development of new treatments, for example for cancer and autoimmune diseases.

Shimon Sakaguchi was swimming against the tide in 1995, when he made the first key discovery. At the time, many researchers were convinced that immune tolerance only developed due to potentially harmful immune cells being eliminated in the thymus, through a process called central tolerance. Sakaguchi showed that the immune system is more complex and discovered a previously unknown class of immune cells, which protect the body from autoimmune diseases.

Mary Brunkow and Fred Ramsdell made the other key discovery in 2001, when they presented the explanation for why a specific mouse strain was particularly vulnerable to autoimmune diseases. They had discovered that the mice have a mutation in a gene that they named Foxp3. They also showed that mutations in the human equivalent of this gene cause a serious autoimmune disease, IPEX.

Two years after this, Shimon Sakaguchi was able to link these discoveries. He proved that the Foxp3 gene governs the development of the cells he identified in 1995. These cells, now known as regulatory T cells, monitor other immune cells and ensure that our immune system tolerates our own tissues.

The laureates’ discoveries launched the field of peripheral tolerance, spurring the development of medical treatments for cancer and autoimmune diseases.

This may also lead to more successful transplantations. Several of these treatments are now undergoing clinical trials.