Nobel Prize in Medicine: This is how the “immune tolerance” that won the 11 million kroner prize works

Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi received the 2025 Nobel Prize in Medicine for explaining how the body avoids attacking itself.

His discovery, valued at 11 million Swedish kronor (about $1 million) , forever changed our understanding of the immune system and opened the door to treatments for autoimmune diseases, cancer, and transplant rejection.

The immune system is a complex defense: it attacks viruses, bacteria, and foreign cells, but it must know when to stop.

If it gets out of control, it can turn against the body itself and cause autoimmune diseases such as type 1 diabetes, lupus, multiple sclerosis , or rheumatoid arthritis.

The work of Brunkow, Ramsdell, and Sakaguchi revealed that there are "regulatory cells" that act as guardians of the immune system, ensuring that it does not damage healthy organs and tissues. This mechanism is called "peripheral immune tolerance."

In 1995, Japanese scientist Shimon Sakaguchi was the first to identify a type of T lymphocyte with an unknown function: suppressing excessive immune responses.

Meanwhile, in the United States, Mary E. Brunkow and Fred Ramsdell discovered in 2001 that a gene called Foxp3 was key to this process. Mice with a mutation in this gene developed severe autoimmune disorders, and the same occurred in human children with a syndrome called IPEX.

Sakaguchi came full circle two years later: he showed that Foxp3 controls the development of regulatory T cells (Tregs) , the same ones he had described years earlier.

Thus was born a new understanding of how the body maintains its own balance.

Peripheral immune tolerance is the body's internal surveillance system.

While the thymus eliminates “rogue” lymphocytes during their maturation (known as “central tolerance”), Tregs act in the periphery, stopping immune cells that could cause autoimmune damage.

In other words: if the immune system were an army, Tregs would be the internal police that prevent soldiers from shooting their own comrades.

Thanks to these findings, therapies are now being developed that seek to strengthen regulatory T cells to treat autoimmune diseases or prevent transplant rejection.

Research is also underway to temporarily block Tregs in cancer patients, allowing the immune system to attack tumors more vigorously.

Several of these treatments are currently in clinical trials and could revolutionize precision medicine.

• Mary E. Brunkow (USA, 1961) – PhD from Princeton University. She directs scientific programs at the Institute for Systems Biology in Seattle.
• Fred Ramsdell (USA, 1960) – PhD in immunology from UCLA, advisor at Sonoma Biotherapeutics and a global leader in cell therapies.
• Shimon Sakaguchi (Japan, 1951) – Physician and researcher at Osaka University. Discoverer of regulatory T cells.

Each will receive 3.67 million Swedish kronor as part of the 2025 Nobel Prize in Physiology or Medicine.

The Nobel Committee summed it up like this:

“Their discoveries were crucial to understanding how the immune system avoids destroying the body it protects.”

This understanding explains why not all of us develop autoimmune diseases, even though our immune systems are active 24 hours a day.

The discovery, although technical, has a very human translation:

Discovering how the body protects itself is understanding how we survive.

What began with a laboratory mouse became one of the most important advances in the modern history of immunology.

Today, “immune tolerance” is not just a concept, but the basis for life-saving treatments that redefine the boundaries between biology and medicine.

The discovery, worth 11 million crowns, represents much more than money: it is the reward for the knowledge that keeps human life in balance.