The Nobel Prize in Medicine 2025 has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries about peripheral immune tolerance. Their work showed how the body prevents its immune system from attacking its own tissues. This discovery opens the door for new treatments for cancer and autoimmune diseases.
The immune system is a remarkable creation that constantly protects us from many microbes. A key challenge for it is identifying invaders while keeping the body’s own cells safe. Although researchers have long understood the idea of central immune tolerance, where harmful T cells are removed in the thymus, the immune system’s complexity is much greater.
What is the Nobel Prize?
The Nobel Prizes, which honor people or organizations whose contributions have had a significant impact on humanity, are widely recognized as some of the most prestigious international honors in the world.
The awards were first given out in 1901 and were established in compliance with the wishes of Swedish inventor, engineer, and chemist Alfred Nobel.
Every Nobel laureate gets:
- An exquisite diploma of recognition.
- A gold medal, signifying excellence.
- . A monetary award, estimated to be worth approximately 11 million Swedish kronor (more than $1 million USD) in 2023.
Although organizations promoting world peace may also receive the Nobel Peace Prize, typically no more than three individuals can share a Nobel Prize.
Finding the Hidden Regulator
Our primary defense is the T cell, which patrols and scans cells for danger using T-cell receptors, of which there are reportedly around quadrillion different shapes. This enormous quantity ensures the detection of novel viruses, but it also implies that certain T cells are capable of identifying the body’s own tissues as well. To control this, a backup system was required.
An earlier experiment that showed that removing the thymus from newborn mice led their immune systems to “run amok” and develop severe autoimmune disorders served as the impetus for Shimon Sakaguchi. Sakaguchi was persuaded that the immune system must contain a “security guard” that soothes other T cells, as he demonstrated in the 1980s that certain isolated T cells could shield mice from certain illnesses.
After more than ten years of research, Sakaguchi designated a completely new type of T cells in 1995. He demonstrated that the protective T cells had both CD4 and CD25 on their surface, even though helper T cells (CD4+) normally stimulate the immune system. He gave these important cells the term “regulatory T cells.”
The Missing Gene: FOXP3
Meanwhile, Mary Brunkow and Fred Ramsdell were studying the mysterious scurfy mouse strain in the US. These male mice had fatal autoimmune disorders caused by a mutation on their X chromosome. Brunkow and Ramsdell knew that understanding this molecular mechanism could offer valuable insights into human autoimmune diseases.
In the 1990s, finding the single faulty gene among the 170 million nucleotides of the X chromosome was a slow process. After years of hard work, they discovered a previously unknown gene and named it FOXP3.
Importantly, they linked mutations in the human version, FOXP3, to the rare autoimmune disease in humans known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome).
Therapeutic Breakthroughs
The mystery was explained after researchers demonstrated that the FOXP3 gene directs the development of Sakaguchi’s regulatory T cells. These cells act like the ultimate security guards that confer peripheral immune tolerance because they stop T cells from damaging healthy tissue.
This foundational observation has opened the door to extraordinarily novel therapeutic possibilities. In the situation of cancer treatment, researchers are trying to break through the wall of regulatory T cells that can surround tumors. In the context of autoimmune diseases and organ therapies, researchers are attempting to induce or expand regulatory T cells – sometimes with interleukin-2 or other similar types of substances – to quiet an overactive immune response that can damage the body’s organs.
