Medicine Nobel 2025 awarded to Brunkow, Ramsdell and Sakaguch for immune tolerance

Every day, the immune system protects humans from thousands of invading microbes—many of which mimic human cells as camouflage. The laureates uncovered how the immune system determines what to attack and what to defend. They identified the immune system’s “security guards,” known as regulatory T cells, which prevent immune cells from turning against the body.

“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” said Olle Kämpe, chair of the Nobel Committee.

Shimon Sakaguchi made the first major discovery in 1995, challenging prevailing scientific thought at the time. Most researchers then believed that immune tolerance developed only through the elimination of harmful immune cells in the thymus—a process known as central tolerance. Sakaguchi, however, demonstrated that the immune system was more complex. He discovered a previously unknown class of immune cells that protect the body from autoimmune diseases.

In 2001, Mary Brunkow and Fred Ramsdell made the next critical breakthrough. They discovered that a specific strain of mice prone to autoimmune diseases carried a mutation in a gene they named Foxp3. They later showed that mutations in the human version of this gene cause a severe autoimmune condition known as IPEX.

Two years later, Sakaguchi linked these findings by proving that the Foxp3 gene governs the development of the cells he had identified in 1995. These cells—now known as regulatory T cells—monitor other immune cells and ensure the body’s immune system tolerates its own tissues.

The laureates’ discoveries laid the foundation for the field of peripheral tolerance, driving the development of new medical treatments for autoimmune diseases and cancer, and offering new hope for improved transplant outcomes. Several of these treatments are currently undergoing clinical trials.