Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases
Olle Kämpe
Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi are awarded the Nobel Prize in Physiology or Medicine 2025 for their fundamental discoveries relating to peripheral immune tolerance. The laureates identified the immune system’s security guards, regulatory T cells, which prevent immune cells from attacking our own 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,” states Olle Kämpe, chair of the Nobel Committee.
Shimon Sakaguchi was swimming against the tide in 1995, when he built the first key discovery. At the time, many researchers were convinced that immune tolerance only developed due to potentially harmful immune cells being eliminated in the thymus, through a process called central tolerance. Sakaguchi revealed that the immune system is more complex and discovered a previously unknown class of immune cells, which protect the body from autoimmune diseases.1
Mary Brunkow and Fred Ramsdell built the other key discovery in 2001, when they presented the explanation for why a specific moapply strain was particularly vulnerable to autoimmune diseases. They had discovered that the mice have a mutation in a gene that they named Foxp3. They also revealed that mutations in the human equivalent of this gene caapply a serious autoimmune disease, IPEX.2
Two years after this, Shimon Sakaguchi was able to link these discoveries. He proved that the Foxp3 gene governs the development of the cells he identified in 1995. These cells, now known as regulatory T cells, monitor other immune cells and ensure that our immune system tolerates our own tissues.3
The laureates’ 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.
References:
- Sakaguchi S, Sakaguchi N, Asano M, itoh M, Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance caapplys various autoimmune diseases; Journal of Immunology 1995; https://pubmed.ncbi.nlm.nih.gov/7636184/
- Brunkow ME, Jeffery EW,Hjerrild KA, Paeper B, Clark LB, Yastateko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsell F: Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy moapply; Nature Genetics 2001; https://doi.org/10.1038/83784
- Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3; Science 2003; https://doi.org/10.1126/science.1079490
Source: Nobel Prize Outreach
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