The Nobel Assembly at the Karolinska Institute in Sweden announced on Monday that the 2025 Nobel Prize in Physiology or Medicine has been awarded to American scientists Mary E. Brunkow of the Institute for Systems Biology and Fred Ramsdell of Sonoma Biotherapeutics, along with Japanese researcher Shimon Sakaguchi of Osaka University.
They were recognized for their ground-breaking discoveries that explain how the immune system regulates itself to avoid attacking the body’s own healthy tissues.
The core idea behind their award-winning work is that while our immune system is powerful and constantly active in defending us against pathogens, if it spins out of control, it can turn inward and attack the body, leading to autoimmune diseases such as type 1 diabetes or severe inflammation affecting multiple organs.
The laureates discovered a crucial safety mechanism called “peripheral immune tolerance,” which is orchestrated by specialized cells known as regulatory T cells (Tregs). These cells act as the immune system’s “brakes,” calming it down when necessary.
Brunkow earned her PhD from Princeton University and is currently a program director at the Institute for Systems Biology in Seattle. Ramsdell holds a PhD from the University of California, Los Angeles, and serves as a scientific advisor at Sonoma Biotherapeutics in San Francisco. Sakaguchi received his doctorate from Kyoto University and is a distinguished professor at the Frontier Research Center for Immunology at Osaka University.
The story began in 1995 with Sakaguchi’s discovery of a previously unknown class of T cells that prevent the immune system from attacking the body. These cells were later named regulatory T cells. In 2001, Brunkow and Ramsdell added another crucial piece to the puzzle. By studying mice that spontaneously developed severe autoimmune diseases, they identified a mutation in a gene they named FOXP3.
Mutations in this gene in humans were later found to cause a rare and life-threatening condition known as IPEX syndrome, characterized by severe immune dysregulation. Two years later, Sakaguchi’s lab demonstrated that FOXP3 is the key switch that enables T cells to become protective regulatory cells.
This series of discoveries provided a clear explanation of how the body maintains immune balance: specialized cells suppress immune responses when they threaten healthy tissue. This understanding has paved the way for a new era of therapies. In cancer, for example, scientists are exploring ways to “release the brakes” so the immune system can attack tumors more aggressively.
In contrast, for autoimmune diseases or organ transplant rejection, researchers aim to strengthen the brakes by boosting or increasing regulatory T cells to calm the immune response. Clinical trials are already underway in both directions.
The Nobel Committee said the three scientists’ work “solved a central mystery: why most people do not suffer from devastating autoimmune diseases.” Their discoveries, the committee added, have been pivotal in understanding immune regulation and have “paved the way for innovative therapeutic strategies.”
