The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their pivotal discoveries in peripheral immune tolerance. This recognition celebrates their foundational work that elucidated how the immune system distinguishes between foreign invaders and the body's own tissues, thereby preventing autoimmune responses. The award ceremony is scheduled for October 6, 2025.
Shimon Sakaguchi's research, which began in 1995, challenged the prevailing understanding that immune tolerance was solely established during immune cell development in the thymus. Sakaguchi's investigations revealed a more complex system, identifying a previously unknown class of immune cells crucial for preventing the body from attacking itself. These cells, now known as regulatory T cells (Tregs), act as the immune system's "security guards," maintaining a delicate balance. Sakaguchi identified these Treg cells in 1995 .
Further significant contributions came from Mary E. Brunkow and Fred Ramsdell in 2001. While working at Celltech Chiroscience, they identified a mutation in the Foxp3 gene in a specific strain of mice, which rendered them highly susceptible to autoimmune diseases. Their subsequent work demonstrated that mutations in the human equivalent of this gene are responsible for IPEX syndrome, a severe autoimmune disorder. Sakaguchi later connected these findings by proving that the Foxp3 gene is essential for the development of the regulatory T cells he had identified, establishing a comprehensive model for peripheral immune tolerance.
The implications of this research are far-reaching. By understanding the mechanisms of peripheral immune tolerance, scientists have opened new avenues for treating a spectrum of conditions, including autoimmune diseases, cancer, and organ transplant rejection. The insights gained have spurred the development of novel therapeutics, with over 200 clinical trials currently underway based on this foundational work. Mary E. Brunkow is a senior program manager at the Institute for Systems Biology in Seattle, and Fred Ramsdell is a scientific advisor at Sonoma Biotherapeutics. Shimon Sakaguchi is a distinguished professor at Osaka University, Japan.