The body’s immune system recruits certain cells to fight infections and help heal wounds. Afterwards, another group of cells will tell those recruits it’s time to stand down. That second group acts as peacemakers, getting an active immune system to calm down. Three scientists who did pivotal work to understand these peacemakers will take home this year’s 2025 Nobel Prize in physiology or medicine.
The Nobel Assembly in Stockholm, Sweden, announced the scientists’ win on October 6. Each winner will get an equal share of 11 million Swedish krona. The full prize is worth more than $1.1 million.
Regulatory T cells, or T-regs, is the formal name of these peacemaker cells. They keep the immune system from attacking healthy tissue. When they fail at this, the body can develop autoimmune disease or damaging inflammation. Peacemaker cells even help keep the body from rejecting a fetus during pregnancy.
Shimon Sakaguchi discovered T-regs while working at Japan’s Kyoto University in 1995. He now works not far from there, at Osaka University.
Also in the 1990s, two other scientists tracked down an altered gene — or mutation — that caused a fatal autoimmune disease. The pair carried out this work on male mouse pups while they were working at Celltech Chiroscience. That’s in Bothell, Wash.
One of these two, Mary Brunkow, now works at the Institute for Systems Biology. It’s in Seattle, Wash. The other, Fred Ramsdell, co-founded Sonoma Biotherapeutics. This company is based in Seattle and San Francisco, Calif.
The mutation this pair studied turns off a gene called FOXP3. Sakaguchi would later show that this gene plays a major role in T-reg development. Without a working FOXP3 gene, there will be too few T-regs to halt overly active immune cells and keep them from causing harm.
In 2001, Brunkow and Ramsdell showed that mutations in this gene are behind IPEX syndrome. It’s an inherited autoimmune disease. Affected people either lack a small group of regulatory T cells or these cells don’t work well. This doesn’t keep the immune system from turning on normally. It will just have trouble turning off. It’s as if the system has no brakes.
Scientists are now learning to harness T-regs. Their goal is to keep the body from rejecting transplanted organs and to treat other conditions in which the immune system is overactive or directed against the wrong thing. These include other autoimmune disorders, food allergies and some cancers.
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