The 2025 Nobel Prize in Physiology or Medicine was awarded to three researchers — Shimon Sakaguchi, Mary E. Brunkow and Fred Ramsdell — for discovering how the immune system is kept in check, based on studies in mice.

Until 1995, it was believed that the immune system avoids attacking the body only by eliminating cells that recognise the body’s own proteins, a process that occurs early in life in the thymus. However, the laureates identified regulatory T cells — immune cells that send signals to calm the immune system when attacking our own cells, thus preventing harm to the body.

Sakaguchi, at Osaka University, performed a key experiment by removing the thymus of newborn mice, which caused them to develop autoimmune diseases. However, when he injected the mice with mature T cells from other mice, they were protected, suggesting that there was another security guard keeping the immune system in check. By performing similar experiments with different types of T cells, he discovered regulatory T cells, the ones responsible for protecting against autoimmunity.

Mary Brunkow and Fred Ramsdell, researchers in the US (1), were working on the effects of radiation when they found a mutation that made T cells attack the body’s own organs in mice. They discovered the gene responsible, Foxp3, and found that mutations in this gene cause IPEX, a rare autoimmune disease in humans.

Two years later, Sakaguchi and other researchers put these discoveries together and showed that the Foxp3 gene controls the development of regulatory T cells.  

“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 and an autoimmunity researcher at EARA member Karolinska Institute.

These fundamental findings are contributing to research on how to prevent organ rejection after transplantation and have paved the way for many treatments for cancer and autoimmune diseases which are now undergoing clinical trials.

(1) Read the highlight from the Foundation for Biomedical Research, US