On October 6, 2025, Mary Brunkow, from the Institute for Systems Biology in Seattle, Fred Ramsdell, from Sonoma Biotherapeutics in San Francisco, and Shimon Sakaguchi, from Osaka University in Japan, were awarded the 2025 Nobel Prize in Physiology or Medicine. The Nobel Prize in Physiology or Medicine has been awarded annually by the Nobel Assembly at the Karolinska Institute since 1901. It is one of the most prestigious awards in the field of science, celebrating discoveries that mark milestones in our understanding of biology and medicine. This year’s prize was awarded for groundbreaking work in peripheral immune tolerance that identified regulatory T (Treg) cells and explained how they prevent immune cells from attacking our own body.
There are three main types of T-cells: helper T-cells, killer T-cells, and regulatory T-cells, which were the focus of this research. Every T-cell has its own unique T-cell receptor that attaches to invading microbes, activating the T-cell and alerting other immune cells. To ensure that different types of invading microbes are detected, the body produces many different T-cell receptors, which ultimately lead to some that will attach to our own tissues.
In the 1980s, researchers believed that the human body only eliminated harmful T cells through a process called central tolerance, which occurs when T cells mature in the thymus. However, in his research published in 1995, Shimon Sakaguchi defined a previously unknown group of immune cells — regulatory T-cells — that protected mice in his study against autoimmune diseases. Then, in 2001, more definitive evidence was presented by Mary Brunkow and Fred Ramsdell. Brunkow and Ramsdell were interested in studying an X chromosome mutation in mice called scurfy, which caused approximately half the male mice to be born with scaly, flaky skin, enlarged spleens and lymph glands, and a shortened lifespan. They decided to identify the specific mutant gene that caused scurfy. With the limited genetic technology of the 1990s, they slowly narrowed down their search range to 500,000 nucleotides in the 170 million base pairs of the X chromosome. After years of dedicated research, they mapped out the potential area and found the previously unknown mutation, naming it Foxp3. In their 2001 report, Brunkow and Ramswell revealed that the mutations in FOXP3 not only cause scurfy in mice, but also IPEX disease in humans. Finally, in 2003, Shimon Sakaguchi proved that the Foxp3 gene controls regulatory T cell development.
Brunkow, Ramsdell, and Sakaguchi’s discoveries have opened the door to a new field of biomedical research and inspired the creation of many therapies. At present, there are more than 200 ongoing clinical trials involving Treg cells, aiming to use this discovery to treat conditions such as cancer and autoimmune disorders.