The Nobel Prize in Physiology or Medicine for 2025 has been awarded to three scientists for their “groundbreaking” discoveries concerning peripheral immune tolerance, which prevents the immune system from harming the body.
Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have been awarded the Nobel Prize in Physiology or Medicine 2025 for their fundamental discoveries relating to peripheral immune tolerance, identifying the immune system’s security guards - regulatory T cells - which prevent immune cells from attacking our own body.
Their discoveries have laid the foundation for a new field of research and spurred the development of new treatments, for example in cancer and autoimmune diseases.
“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.
The thousands of microbes that attempt to attack the human body on a daily basis all have different appearances, and many have developed similarities with human cells in an attempt to camouflage themselves, leading researchers to look at how the immune system determines what to attack and what to protect.
In 1995 Sakaguchi discovered a previously unknown class of immune cells, which protect the body from autoimmune diseases. Brunkow and Ramsdell made the other key discovery in 2001, explaining why a specific mouse strain was particularly vulnerable to autoimmune diseases, discovering that the mice have a mutation in a gene that they named Foxp3.
Two years later Sakaguchi linked these discoveries. He proved that the Foxp3 gene governs the development of the cells he identified in 1995. These cells, the regulatory T cells, monitor other immune cells and ensure that our immune system tolerates our own tissues.
The 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.
Current ongoing research includes understanding tumours that can attract large numbers of regulatory T cells that protect them from the immune system. Researchers are now trying to find ways to dismantle this shield so the immune system can access the tumours. In contrast in autoimmune diseases, researchers are instead trying to promote the formation of more regulatory T cells.
Sakaguchi is distinguished professor at the Immunology Frontier Research Center, Osaka University, Japan. Brunkow is a senior program manager at the Institute for Systems Biology, Seattle, US, and Ramsdell is a scientific advisor at Sonoma Biotherapeutics, San Francisco, US.
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