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This year’s Nobel Prize laureates in physiology or medicine discovered how the immune system is kept in check.

Our immune system is an evolutionary masterpiece. Every day it protects us from the thousands of different viruses, bacteria and other microbes that attempt to invade our bodies. Without a functioning immune system, we would not survive.

One of the immune system’s marvels is its ability to identify pathogens and differentiate them from the body’s own cells. The microbes that threaten our health do not wear a uniform – they all have different appearances. Many have also developed similarities to human cells, as a form of camouflage. So how does the immune system keep track of what to attack and what to protect? Why doesn’t the immune system attack our bodies more frequently?

Researchers long believed they knew the answer to these questions: that immune cells mature through a process called central immune tolerance. However, our immune system turned out to be more complex than they believed. Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have been awarded the 2025 Nobel Prize in Physiology or Medicine for their discoveries concerning peripheral immune tolerance.

The Nobel Prize laureates identified the immune system’s security guards, regulatory T cells, thus laying the foundation for a new field of research. The discoveries have also led to the development of potential medical treatments that are now being evaluated in clinical trials. The hope is to be able to treat or cure autoimmune diseases, provide more effective cancer treatments and prevent serious complications after stem cell transplants.

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BREAKING NEWS
The Nobel Assembly at Karolinska Institutet has decided to award the 2025 Nobel Prize in Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

This year’s medicine laureates have discovered how the immune system is kept in check. The body’s powerful immune system must be regulated, or it may attack our own organs. Brunkow, Ramsdell and Sakaguchi have been awarded this year’s medicine prize for their groundbreaking discoveries concerning peripheral immune tolerance that prevents the immune system from harming the body.

The laureates identified the immune system’s security guards, regulatory T cells, which prevent immune cells from attacking our own body.

The laureates’ discoveries launched the field of peripheral tolerance, spurring the development of medical treatments for cancer and autoimmune diseases. This may also lead to more successful transplantations. Several of these treatments are now undergoing clinical trials.

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The 2025 medicine laureates identified the immune system’s security guards, regulatory T cells, which prevent immune cells from attacking our own body.

The fundamental knowledge that researchers have gained through the discovery of regulatory T cells and their importance for peripheral immune tolerance, has spurred the development of potential new medical treatments. Mapping of tumours shows that they can attract large numbers of regulatory T cells that protect them from the immune system. Researchers are therefore trying to find ways to dismantle this wall of regulatory T cells, so the immune system can access the tumours.

In autoimmune diseases, researchers are instead trying to promote the formation of more regulatory T cells. In pilot studies, they are giving patients interleukin-2, a substance that makes regulatory T cells thrive. Researchers are also investigating whether interleukin-2 can be used to prevent organs being rejected after transplantation.

Another strategy researchers are testing to slow an overactive immune system is to isolate regulatory T cells from a patient and multiply them in a laboratory. These are then returned to the patient, who will thus have more regulatory T cells in their body. In some cases, researchers also modify the T cells, putting antibodies on their surface that function like an address label. This allows researchers to send these cellular security guards to a transplanted liver or kidney, for example, and protect the organ from being attacked by the immune system.

There are many more examples of how researchers are testing how regulatory T cells can be used to combat diseases. Through their revolutionary discoveries, Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have provided fundamental knowledge of how the immune system is regulated and kept in check. They have thus conferred the greatest benefit to humankind.

The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

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During pregnancy, fetal cells migrate out of the womb and into a mother’s heart, liver, lung, kidney, brain, and more. They could shape moms’ health for a lifetime, Katherine J. Wu reported in 2024:⁠ https://theatln.tc/qozjIdje
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The presence of these cells, known as microchimerism, is thought to affect every person who has carried an embryo, even if briefly, and anyone who has ever inhabited a womb. The cross-generational transfers are bidirectional—as fetal cells cross the placenta into maternal tissues, a small number of maternal cells migrate into fetal tissues, where they can persist into adulthood. ⁠
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Genetic swaps, then, might occur several times throughout a life. Some researchers believe that people may be miniature mosaics of many of their relatives, via chains of pregnancy: their older siblings, perhaps, or their maternal grandmother, or any aunts and uncles their grandmother might have conceived before their mother was born. “It’s like you carry your entire family inside of you,” Francisco Úbeda de Torres, an evolutionary biologist at the Royal Holloway University of London, told Wu.⁠
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Some scientists have argued that cells so sparse and inconsistent couldn’t possibly have meaningful effects. Even among microchimerism researchers, hypotheses about what these cells do—if anything at all—remain “highly controversial,” Sing Sing Way, an immunologist and a pediatrician at Cincinnati Children’s Hospital, told Wu. But many experts contend that microchimeric cells aren’t just passive passengers. They are genetically distinct entities. And they might hold sway over many aspects of health: our susceptibility to infectious or autoimmune disease, the success of pregnancies, maybe even behavior. ⁠
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If these cells turn out to be as important as some scientists believe they are, they might be one of the most underappreciated architects of human life, Wu writes.

“Your purpose as a scientist is not to achieve fame or money, that is not your purpose, those might be side effects and good for you, that could be wonderful for you but it is a side effect, it is not the main goal. The main goal is to make discoveries and gift them to humanity. And those discoveries and that knowledge stays with humanity long after you are gone.”

- Carolyn Bertozzi on the scientist's purpose

Meet chemist and 2022 Nobel Prize laureate Bertozzi in our podcast where she speaks about her love of science and music.

Listen here: https://www.nobelprize.org/prizes/chemistry/2022/bertozzi/podcast/

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