Nobel prize in medicine awarded to trio for immune tolerance work
The 2025 Nobel prize in physiology or medicine has been awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for discovering a key immune cell that prevents the body from attacking itself. Their work revealed regulatory T-cells and the FOXP3 gene's role in controlling autoimmune responses. This breakthrough has opened new avenues for treating autoimmune diseases and cancers.
The Nobel Assembly at the Karolinska Institute announced the 2025 prize on October 7, recognizing the trio's contributions to understanding immune tolerance. Immune cells known as T-cells are essential for fighting viruses and bacteria, but they can sometimes target the body's own proteins, leading to autoimmune conditions like type 1 diabetes and rheumatoid arthritis.
T-cells develop in the bone marrow and mature in the thymus, where a selection process eliminates many self-reactive ones. However, in 1995, Shimon Sakaguchi, now at Osaka University in Japan, demonstrated through mouse experiments that additional protective mechanisms exist in the bloodstream. He found that removing the thymus post-birth caused autoimmune diseases in mice, but injecting T-cells from healthy mice prevented this. Sakaguchi identified these protective cells as CD25 regulatory T-cells, marked by a surface protein.
Meanwhile, Mary Brunkow, now at the Institute for Systems Biology in Seattle, Washington, and Fred Ramsdell, a scientific adviser at Sonoma Biotherapeutics in San Francisco, California, examined mice prone to autoimmunity. In 2001, they discovered a mutation in the FOXP3 gene on the X chromosome in these animals. Humans with FOXP3 mutations suffer from IPEX syndrome, increasing autoimmune disease risk.
In 2003, Sakaguchi linked the discoveries, showing FOXP3's crucial role in developing CD25 regulatory T-cells. "It unleashed a whole new field in immunology," said Marie Wahren-Herlenius at the Karolinska Institute. Earlier skepticism about Sakaguchi's findings was resolved by Brunkow and Ramsdell's work, according to Wahren-Herlenius.
These insights could transform treatments: boosting regulatory T-cells might suppress autoimmune reactions, while reducing them could enhance anti-cancer immunity. Several clinical trials are exploring these applications. "Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases," stated Olle Kämpe, chair of the Nobel committee.