Explainer: Why 2025 Nobel in Medicine awards immune system's "security guards"

STOCKHOLM, Oct. 7 (Xinhua) -- Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi won the 2025 Nobel Prize in Physiology or Medicine on Monday for discoveries that explain how the immune system is kept in check to prevent attacks on the body's own organs.

The Nobel Assembly at Sweden's Karolinska Institutet cited their work "for their discoveries concerning peripheral immune tolerance," awarding a prize of 11 million Swedish kronor (1.17 million U.S. dollars) to be shared equally between the laureates.

WHO ARE THEY AND WHAT THEY FOUND?

The immune system is a marvel of intricate checks and balances, enabling robust defences against infections while, in most cases, avoiding destructive responses against the body's own tissues. How this balance is maintained has puzzled immunologists for more than a century.

For decades, researchers long believed that "immune tolerance" was enforced mainly in the thymus, where self-reactive T cells are eliminated during development, a process known as central tolerance. That view left a puzzle: despite this early culling, harmful immune reactions still arose unless something else kept mature T cells in check.

In the mid-1990s, Sakaguchi showed what that "something else" was. He identified a small subset of T cells marked by proteins called CD4 and CD25 that act as brakes on immunity: removing them from mice triggered autoimmune disease, and restoring them calmed the attack. He named these cells regulatory T cells (Tregs).

In 2001, U.S. researchers Brunkow and Ramsdell traced a severe autoimmune syndrome in the "scurfy" mouse strain to mutations in a previously unknown gene they named Foxp3. They also showed that mutations in the human equivalent of the gene, FOXP3, can cause IPEX syndrome, a rare and often fatal pediatric disorder marked by multi-organ autoimmunity.

Follow-up work in 2003 established that FOXP3 is the control switch for Tregs. Together, these findings connected the cells and the gene into a single mechanism -- peripheral immune tolerance -- that continually polices harmful immune reactions outside the thymus.

WHY THE DISCOVERIES MATTER?

The work overturned the long-held assumption that the thymus' early "weeding out" of self-reactive cells was sufficient. It revealed a second line of defense, peripheral immune tolerance, in which Tregs continually prevent friendly fire and help the system "stand down" once invaders are cleared.

Through their revolutionary discoveries, the trio has provided fundamental knowledge of how the immune system is regulated and kept in check, said the Nobel Assembly in a release, adding that the outcome conferred the greatest benefit to humankind.

"Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases," says Olle Kampe, chair of the Nobel Committee.

Qiang Pan-Hammarstrom, member of the Nobel Committee, told Xinhua that the award is "for a major scientific discovery" rather than a finished treatment.

She said the work "clinched the case" that FOXP3 is the lineage-defining switch for Tregs by linking the scurfy mouse to IPEX in humans.

WHAT COULD IT MEAN FOR PATIENTS?

According to Pan-Hammarstrom, the trio's work has had far-reaching clinical implications, paving the way for new treatments for autoimmune diseases and cancer, and potentially improving the success of transplantations.

In autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, the aim is to restore or strengthen the body's own Tregs so they stop mistaken attacks on organs. In transplantation, the same cells could help patients accept a new organ with fewer broad immunosuppressants.

In cancer, where tumours can accumulate Tregs to blunt immune attack, researchers are testing ways to reduce those cells inside the tumour so treatment works better.

Pan-Hammarstrom said parts of these approaches are already in more than 200 clinical trials worldwide, including efforts by companies in China, but most studies are still in early to mid-stages, and none have reached Phase III. Enditem