Shimon Sakaguchi, Mary Brunkow, and Fred Ramsdell Awarded 2025 Nobel Medicine Prize for Immune Tolerance Discoveries

Groundbreaking Discoveries in Immune System Regulation Honored

The 2025 Nobel Prize in Physiology or Medicine has been jointly awarded to Shimon Sakaguchi of Japan, and Americans Mary E. Brunkow and Fred Ramsdell. The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, announced the laureates on Monday, October 6, 2025, recognizing their 'discoveries concerning peripheral immune tolerance' . Their pioneering research into regulatory T cells has fundamentally reshaped the understanding of how the immune system maintains balance and prevents self-attack, paving the way for novel therapeutic strategies against autoimmune diseases, cancer, and complications in organ transplantation .

Unveiling the Immune System's 'Security Guards'

The immune system, a powerful defense mechanism, must be meticulously regulated to prevent it from attacking the body's own organs . For decades, researchers believed that immune tolerance was primarily established by eliminating harmful immune cells in the thymus . However, Shimon Sakaguchi, a distinguished professor at Osaka University's Immunology Frontier Research Center, challenged this view with his pivotal discovery in 1995 . He identified a previously unknown class of immune cells, which he termed regulatory T cells (Tregs), that actively suppress immune responses and protect the body from autoimmune diseases . These cells act as the 'security guards' or 'brakes' of the immune system, ensuring it distinguishes between foreign invaders and the body's own tissues .

The Critical Role of the FOXP3 Gene

Adding another crucial piece to the puzzle, Mary E. Brunkow, a senior program manager at the Institute for Systems Biology in Seattle, and Fred Ramsdell, a scientific adviser for Sonoma Biotherapeutics in San Francisco, made a significant breakthrough in 2001 . They discovered the FOXP3 gene, which is essential for the development and function of regulatory T cells . Their research revealed that mutations in this gene lead to severe autoimmune disorders in both mice and humans, including a rare condition known as IPEX syndrome . Sakaguchi later conclusively demonstrated that the FOXP3 gene controls the formation and function of the regulatory T cells he had identified .

Impact on Medicine and Future Therapies

The collective discoveries of Sakaguchi, Brunkow, and Ramsdell have laid the foundation for a new field of research known as peripheral immune tolerance . This fundamental knowledge has spurred the development of potential new medical treatments, many of which are currently undergoing clinical trials . These include efforts to:

• Increase regulatory T cells to suppress unwanted immune reactions in autoimmune diseases like Type 1 diabetes, rheumatoid arthritis, and lupus, or following organ transplantation .
• Decrease regulatory T cells in cancer treatment, as cancer cells can exploit Tregs to evade the immune system .

The laureates' work has provided critical insights into how the immune system functions, offering new hope for controlling a range of debilitating diseases and improving human health .

Recognition and Shared Honor

The three scientists will share the prize money of 11 million Swedish kronor (approximately £871,400) . Upon the announcement, Japanese Prime Minister Shigeru Ishiba extended his congratulations to Professor Sakaguchi . The Nobel Committee emphasized that their discoveries have been 'decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases' .