The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow (USA), Fred Ramsdell (USA), and Shimon Sakaguchi (Japan) for pioneering research into how the immune system is regulated so that it does not attack the body itself. The announcement was made by the Nobel Assembly at Karolinska Institutet on 6 October.
What They Discovered
The trio’s work centres on peripheral immune tolerance — mechanisms that ensure immune cells do not mistakenly attack healthy tissues. Two major pieces of this puzzle were uncovered: Shimon Sakaguchi, in 1995, identified a type of immune cell called regulatory T cells (often called “Tregs” or regulatory T-cells), which function as “security guards” by suppressing harmful immune reactions that might target the body’s own cells. NobelPrize.org+2NobelPrize.org+2
Mary Brunkow and Fred Ramsdell, in 2001, discovered that a gene called FOXP3 is critical for the development and function of these regulatory T cells. They found a mutation in this gene in mice (and corresponding human cases) that leads to severe autoimmune conditions.
Together, these findings showed that immune tolerance is not just about removing harmful immune cells early on (in the thymus, a process known as “central tolerance”) but also involves ongoing regulation throughout life — in the body at large (“peripheral tolerance”) — to prevent autoimmune disease.
Why It Matters
Understanding Autoimmune Diseases: Many conditions (like Type 1 diabetes, lupus, rheumatoid arthritis) happen when the immune system mistakenly attacks its own tissues. The discoveries by Brunkow, Ramsdell, and Sakaguchi provide the molecular and cellular explanation for how such self-attack is normally prevented.
New Therapeutic Avenues: With regulatory T cells and FOXP3 as known factors, there is potential for developing treatments that enhance or mimic these regulatory mechanisms. For example, in treating autoimmune diseases, improving outcomes in transplants, or possibly modulating immune responses in cancer. Clinical trials are underway in some related areas.
Balancing Immune Activation and Suppression: Modern immunology often focuses on activating immune responses (e.g., against infections or cancer). But unchecked activation can lead to damage. These discoveries highlight the equally important side: how the body keeps immune responses in check.
Details & Reactions
The prize sum is 11 million Swedish kronor, to be shared equally among the three laureates.
The Karolinska Institute stated that their work “has been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases.”
The discoveries date back decades: initial identification of regulatory T cells in the mid-1990s, followed by work linking FOXP3 and showing the consequences of its dysfunction in the early 2000s.
In all, the 2025 Medicine Nobel Prize honours work that deepens our understanding of immune regulation, not just how the immune system attacks, but how it restrains itself, and how balance is maintained. As scientists build on these foundations, there’s hope for better treatments for autoimmune disease, safer transplantation, and immunotherapies with fewer side effects.