Nobel Prize in Medicine awarded for advances in immune research

The US researchers Mary E. Brunkow and Fred Ramsdell and the Japanese Shimon Sakaguchi receive the award for their fundamental work on regulatory T cells that prevent autoimmune diseases.

The Nobel Prize in Physiology or Medicine in 2025 will go to three researchers who have identified the “security forces” of the immune system. As announced by the Nobel Committee at the Karolinska Institute in Stockholm, the US-American Mary E. Brunkow, the US-American Fred Ramsdell, and the Japanese Shimon Sakaguchi will be honored for their discoveries on “peripheral immune tolerance.” Their research explains how the immune system is prevented from attacking its body and opens up new ways of treating autoimmune diseases and cancer.

The immune system faces the daily challenge of differentiating between the body's own cells and foreign invaders such as viruses or bacteria. If this control mechanism fails, it can lead to severe autoimmune diseases in which immune cells attack healthy organs and tissue. This year's prizewinners have discovered the main cellular players in this control system: regulatory T cells.

The decisive discoveries

Shimon Sakaguchi from Osaka University set the first milestone back in 1995 when, contrary to the prevailing doctrine at the time that immune tolerance arises exclusively in the thymus through the elimination of potentially harmful immune cells (central tolerance), he proved the existence of another control instance. He discovered a previously unknown class of immune cells that actively protect the body from autoimmune reactions.

The second decisive contribution was made in 2001 by Mary E. Brunkow (Institute for Systems Biology, Seattle) and Fred Ramsdell (Sonoma Biotherapeutics, San Francisco), who investigated a mouse strain that was particularly susceptible to autoimmune diseases and found the cause in a mutation of a gene they called Foxp3. They were also able to show that mutations in the human counterpart of this gene trigger the severe autoimmune disease IPEX.

Two years later, Sakaguchi succeeded in linking these two discoveries. He proved that the Foxp3 gene identified by Brunkow and Ramsdell controls the development and function of the cells he had discovered in 1995. These cells are now known as regulatory T cells. They act as sentinels that monitor other immune cells and ensure that the immune system tolerates its tissues.

Basis for new therapies

“Their discoveries were crucial to our understanding of how the immune system works and why we do not all develop severe autoimmune diseases,” said Olle Kämpe, Chairman of the Nobel Committee, in recognition of the work of the honorees.

The research of the three laureates has established the field of peripheral tolerance and significantly advanced the development of therapies for autoimmune diseases and cancer. The findings could also play an important role in more successful organ transplants. Several treatments based on these discoveries are already in clinical trials.

The prize money totaling 11 million Swedish kronor (around 950,000 euros) will be divided equally between the three winners. The award ceremony will take place on 10 December, the anniversary of Alfred Nobel's death, at Stockholm City Hall.

(mki)