The 2025 Nobel Prize in medicine or physiology was awarded to three scientists who discovered how to stop the immune system of the body from attacking itself.
Shimon Sakaguchi, from Osaka University, Japan, Mary E. Brunkow, from the Institute for System Biology, and Fred Ramsdell, from Sonoma Biotherapeutics in the USA have identified “security guards” that help keep the immune system under control. The discoveries are important in understanding how to prevent and treat autoimmune diseases. Each of the three will receive a share of a total prize amounting to 11 million Swedish Kronors (around PS870,000).
A healthy immune system is essential. The immune system sculpts the tissues and removes old cells as they develop. This also helps to keep us healthy by eliminating harmful viruses, bacteria, and fungi.
The immune system is faced with a difficult challenge. It must fight thousands of microbes every day. Many of these have developed to look very similar to the cells of our body. But it cannot mistake its own tissues for an enemy.
How does the immune cell know which cells to attack?
Immunologists have been studying this question for many decades. The Nobel Laureates’ groundbreaking research led to the discovery that specialised immune cell called regulatory T-cells prevent immune cells attacking the body, and keeps the immune system functioning as it should.
Immunologists didn’t know why certain immune cells worked as they should and others attacked their own tissue for decades. This can lead to autoimmune diseases such as type I diabetes, rheumatoid arthritis and multiple sclerosis.
Scientists believed for a very long time that the small gland located in the chest, the thymus, was responsible solely for immunity tolerance. Scientists believed that immune cells, specifically a cell type called T lymphocytes, which recognized the body’s proteins too strongly would be removed from the thymus during early childhood. The immune cells with mild reactions were released to the bloodstream and patrolled the body.
Sakaguchi’s research in the 1980s & 1990s showed that a special class of T-cells played an important role in suppressing the immune response and stopping the immune system attacking tissues.
Sakaguchi performed his first experiment by surgically removing the thymus from mice born at birth, and then injecting T cells from mice with genetically identical genes. The hypothesis was that mice with a weaker immunity would develop fewer cells.
He discovered, instead, that the T cells appeared to protect mice against developing autoimmune disease.
Sakaguchi spent the following decade trying to determine if there are different T cell types that play different roles during immune responses. Sakaguchi’s 1995 paper described a class of “regulatory” T cells. The paper showed that T-cells with a certain type of surface protein actually eliminate harmful T cells.
Scientists were initially sceptical about regulatory T-cells. Brunkow’s and Ramsdell’s work published between the 1990s to early 2000s demonstrated how regulatory T-cells function.
The research of Brunkow and Ramsdell showed that regulatory cells stop immune cells attacking the body either by secreting immuno-dampening proteins, or directly by delivering antiinflammatory signals.
The researchers also identified a protein (called FoxP3) that helped identify these T-cells. Scientists could now determine when a T cell is regulatory, and isolate it for further study.
The findings showed that regulatory T cells, also called T-regs in short form, are important in controlling other immune cells.
This year’s Nobel Laureates have also opened the field of Immunology, which has gone far beyond simply understanding immune tolerance.
They have shown that inflammation and immunity are actively controlled. The work has led to a number of novel ideas for controlling inflammatory diseases, caused by infections, allergens or environmental pollutants, as well as autoimmunity.
The research has also provided novel ideas for preventing transplant rejection and improved immune response to cancer treatment and vaccines.
