Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi are winners for their discoveries on peripheral immune tolerance, a fundamental advance that could transform the fight against autoimmune diseases and improve transplants.
Regulatory T lymphocytes, moderators of our immune defenses
On October 6, 2025, the Nobel Assembly awarded the Nobel Prize for Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi for their work on peripheral immune tolerance (the main sources are the press release from Karolinska Institute and the Nobel Prize notice). This research describes an active mechanism which prevents the immune system from attacking healthy tissues outside the thymus, that is to say in the circulation and organs of the body.
Concretely: in the 1990s, Shimon Sakaguchi identified a population of immune cells (marked CD4+ CD25+) playing a brake role. Subsequently, Mary Brunkow and Fred Ramsdell set the FoxP3 gene to the day by studying mice in the “scurfy” phenotype – a mutation resulting in uncontrolled immune reactions. These discoveries were linked when it appeared that FoxP3 regulates the development and function of these so -called regulatory cells (Tregs).
As Olle Kämpe, President of the Nobel Committee summed up: “Their discoveries have been decisive for our understanding of the functioning of the immune system and the reason why we do not all develop autoimmune diseases serious serious“.
Real hope in the face of autoimmune diseases
Our immune system is a complex orchestra, where each cell must play its score. The Tregs are like a silent conductor: without them, the other cells can be unleashed against the tissues of the body. Tregs therefore work as moderators: they inhibit excessive immune responses and maintain “peace” between defense and tolerance. When they lack – by mutation of the FOXP3 gene or by deteriorating their activity – the risk of the appearance of autoimmune diseases increases sharply. Among the affections concerned are type 1 diabetes, multiple sclerosis and rheumatoid arthritis.
On the therapeutic level, the discovery of TREGS opens two main axes: locally strengthen these cells to calm an autoimmune disease, or modulate their activity to improve the efficiency of anti-cancer treatments without causing self-aggression. Moreover, many clinical trials (more than 200 according to the Nobel Committee) already explore treatments based on peripheral tolerance.
But the path is still long:
- These regulatory cells must be avoided not harm defense against infections or cancers;
- Control their locality: Tregs must act in the right fabrics, at the right time;
- Understand the complex molecular signals that activate or inhibit them.
Nevertheless, this discovery offers a new way of hope for millions of patients who live with a silent war inside their bodies.
The award of a scientific breakthrough and the promise of clinical applications
This Nobel Prize is part of a tradition: that of rewarding discoveries that redefine our understanding of the body. In the past, several Nobel prizes have been awarded for immunity, antibodies, the presentation of antigens, but never for this silent mechanism of peripheral regulation.
Brunkow, Ramsdell and Sakaguchi thus join these prestigious names by introducing a new dimension – less spectacular in appearance, but vital in daily life. Their discovery bridges between fundamental biology and applied medicine.
Their work could have repercussions on the management of transplants – by limiting discharges – and on the modulation of cancer treatments, where the border between tolerance and anti -tumor reaction is particularly delicate. In short, this Nobel rewards not only a scientific breakthrough, but a promise: that of better understanding our body to better protect it.