2025 Nobel Prize in Medicine to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for identifying the "security guards of the immune system."

The Karolinska Institute in Stockholm, Sweden, awarded the Nobel Prize in Physiology or Medicine on Monday to American scientists Mary Brunkow and Fred Ramsdell, and to Japanese scientist Shimon Sakaguchi, " for their discoveries concerning peripheral immune tolerance." The laureates identified the "security guards of the immune system," regulatory T cells, which prevent the immune system from attacking our own bodies, according to the committee.

"Their discoveries have been fundamental to our understanding of how the immune system works and why not all humans develop autoimmune diseases," explained Olle Kämpe, president of the jury.

The key discovery in this field was made by Japanese immunologist Shimon Sakaguchi in 1995. After years of unrecognized research in his field, he was the first to isolate these regulatory T cells, a type of essential lymphocyte that modulates the activity of the immune system and protects the body from autoimmune diseases. Until then, most researchers were convinced that immune tolerance only developed because potentially harmful immune cells were eliminated in the thymus, through a process called central tolerance. This gland, located in the chest, below the sternum, is where the different types of lymphocytes, or white blood cells, that form part of the adaptive immune system that protects us from infections, pathogens, and other external aggressions, are generated and matured. The 74-year-old researcher from Osaka University receives one-third of the award for this discovery.

Americans Mary Brunkow, 61, and Fred Ramsdell, 60, share the award for their research into autoimmune diseases, specifically the Foxp3 gene. The scientists discovered a mutation in this gene that increased the risk of autoimmune diseases in laboratory mice. Brunkow, a molecular biologist, and Ramsdell, an immunologist, showed that other mutations in this gene cause serious autoimmune diseases in humans. Brunkow currently works at the Institute for Systems Biology in the United States. Ramsdell is a scientific advisor to Sonoma Biotherapeutics , the company he co-founded in 2019 in the United States to develop treatments for rheumatoid arthritis and other autoimmune diseases based on regulatory T cells.

Following these findings, Sakaguchi demonstrated that this gene governs the production of regulatory T cells, which he named. This is an essential component for the rest of the immune system to tolerate the body's own tissues and not attack them.

The jury emphasized that the work of these three scientists has opened a new field and brings new treatments for cancer and autoimmune diseases closer to reality. Currently, these regulatory cells extracted from the thymus have been essential in preventing transplant rejection, and clinical trials are already underway to demonstrate their effectiveness as a generalized treatment.

Living proof of the importance of this discovery is Irene, a five-year-old Spanish girl who was the first in the world to receive treatment with regulatory T cells to make the heart transplant she needed possible. The key was not to discard the thymus after surgery, as was usually done, but to use it as a source of cells that were later used for treatment.

The same procedure has already been used in nine transplanted babies, explains Dr. Rafael Correa, director of the Immunoregulation Laboratory at Gregorio Marañón Hospital in Madrid. "We have demonstrated that it is a safe, effective therapy capable of preventing acute rejection after a transplant, as it restores immune tolerance," he emphasizes. These cells "have immense potential" as a treatment, Correa emphasizes, for many immune-mediated diseases such as diabetes, allergies, as well as neurodegenerative and autoimmune diseases.

Unlike other lymphocyte therapies, such as CAR-T cells, in this case the cells extracted from the patient are not modified, as they fully retain their ability to modulate the immune system and prevent negative reactions. This makes it possible to use thymus tissue extracted from infants as a source of cells not only for the infants themselves, but potentially also for other adult patients, a therapy that Correa's team is already testing in a pioneering clinical trial.

“It's increasingly clear that immunology is related to almost every disease we can think of, and this Nobel Prize is proof of that,” emphasizes Marcos López-Hoyos, president of the Spanish Society of Immunology. “Our immune response is like a juggler, as it must activate and respond to any external aggression, but also shut down to maintain balance. In this, peripheral immunity generated by regulatory T cells is essential,” explains the immunologist.

The physician and researcher emphasizes that until 1995, "no one" supported the Japanese scientist Sakaguchi's thesis. After his seminal discoveries, the existence of these regulatory cells became widely accepted, and today, "all immunologists study their genetic characteristics due to their important role in regulating" the immune system," he adds.

Since 1901, the Nobel Prize in Physiology or Medicine has recognized 229 researchers, 14 of whom have been women.

Last year, American researchers Victor Ambros and Gary Ruvkun received the prize for discovering microRNAs and describing their role in "post-transcriptional gene regulation." The discovery by Ambros, a researcher at the University of Massachusetts (United States), and Ruvkun, affiliated with Massachusetts General Hospital, reveals a completely new principle of genetic regulation essential for the development and functioning of multicellular organisms, including humans. In 2023, it was awarded to Katalin Karikó and Drew Weissman for the COVID vaccine, and in 2022 to Svante Pääbo for unraveling the genetics of extinct humans.

As of Monday, 115 awards had already been presented in the Medicine category. This will be the first award to be presented this week, followed by the Physics award on Tuesday and the Chemistry award on Wednesday. Each award is worth 11 million Swedish kronor, approximately one million euros.