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2025 Nobel Prize in Physiology or Medicine.

The Nobel Prizes are awards given by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". This year makes it 123 years since the prizes were first awarded. The Nobel Prizes are widely regarded as the most prestigious awards available in their respective fields. The 5 fields covered are physics, chemistry, physiology or medicine, literature and peace. In the 1968, Sweden’s central bank in memory of Alfred Nobel established a sixth prize, the prize in Economic Sciences. Rewards that come with this award and recognition include a gold plated green gold medal, a diploma and a monetary award of approximately $1.035M as of 2023. Each award is not given to more than 3 recipients at a time.

Of the 9 researchers who will head to Stockholm in December for the awards ceremony, Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi will be jointly awarded the 2025 Nobel Prize in Physiology or Medicine for ‘immune tolerance’ research.
According to the prize-awarding body, "their work has advanced our understanding of how the body’s immune system is regulated to prevent it from attacking it’s own organs. Their discoveries have laid the foundation for a new field of research and spurred the development of new treatments, for example, for cancer and autoimmune diseases."
Everyday, our immune system protects us from thousands of invading microbes. However, many pathogens mimic human cells to evade detection, making it crucial for the immune system to differentiate between foreign threats and it’s own tissues. The laureate’s research on peripheral immune tolerance has revealed the role of a special class of immune cells called regulatory T cells. These cells act as guardians against autoimmune diseases.

In 1995, Shimon Sakaguchi challenged the prevailing view that immune tolerance was solely maintained by eliminating harmful immune cells in the thymus. His research showed that the immune system was more complex than previously thought and identified an entirely new type of immune cell, regulatory T cells. These were found to protect the body from autoimmune disorders, marking a breakthrough in immunology.

In 2001, Mary Brunkow and Fred Ramsdell advanced the field through genetic research. They studied mouse strain prone to autoimmune disease and found a mutation in a gene they named Foxp3. This mutation disabled the immune system’s regulatory controls, leading to severe illness. Notably, they confirmed that mutations in the human equivalent of Foxp3 cause IPEX syndrome, a rare but serious autoimmune condition.

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2 years later, Sakaguchi connected dots by proving that the Foxp3 gene orchestrates the development of regulatory T cells. According to the chairman of the Nobel committee, Olle Kampe, "their discoveries have been decisive for our understanding of why we do not all develop serious autoimmune diseases."

The concept of peripheral tolerance now underpins emerging therapies for autoimmune diseases, cancer and organ transplantation. Several Foxp3 based therapies are already in clinical trials, with hopes of improving patient outcomes and enabling more successful transplants.

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