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This year’s Nobel laureates in Physiology or Medicine have discovered what helps our immune system avoid turning against itself. Thanks to the work of Mary E. Brankov, Frederic Ramsdell, and Shimon Sakaguchi, we now better understand how the body distinguishes “self” from “non-self” — and why not all of us develop autoimmune diseases. Their discovery already influences the development of new treatments for cancer and diabetes, as well as the future of transplantation. How exactly this discovery is changing medicine and why every medical student should know about it is explained by Tetiana Liadova, Dean of the First School of Medicine at Karazin University.
— Tetiana Ivanivna, could you please tell us more about who received the Nobel Prize in Physiology or Medicine in 2025 and for what discovery?
The 2025 Nobel Prize in Physiology or Medicine was awarded to three scientists — Mary Elizabeth Brankov, Frederic Ramsdell, and Shimon Sakaguchi. They were recognized for a discovery that changed our understanding of how the human immune system works. In their research, they described a mechanism known as peripheral immune tolerance — the process that allows the immune system to distinguish the body’s own cells from foreign ones, maintaining a balance between defense and self-control.
For a long time, it was believed that the main control of immune responses occurred in the thymus, where T-lymphocytes capable of recognizing the body’s own tissues were destroyed during maturation. However, even in healthy people, some cells remain that could potentially trigger autoimmune reactions. The scientists proved that the body has another equally important level of control that operates outside the thymus — in the periphery of the immune system.
Shimon Sakaguchi was the first to describe a special group of T-lymphocytes known as regulatory T cells (Tregs). Their main function is to suppress excessive immune activity so that the immune system does not begin to attack the body’s own tissues. Mary Brankov and Frederic Ramsdell discovered the FOXP3 gene, which governs the development and functioning of these cells. It turned out that when this gene is damaged, regulatory T cells fail to develop, and the body loses its ability to control its own immune responses. This discovery explained the causes of severe autoimmune syndromes accompanied by inflammation of multiple organs.
Thanks to this research, it became clear that the immune system not only attacks what is foreign but also constantly regulates itself. The balance between activation and inhibition is essential for health. This knowledge opened new possibilities for treating autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Around the world, clinical studies are now exploring the use of regulatory T cells to suppress undesirable immune reactions and prevent transplant rejection.
The discovery by Brankov, Ramsdell, and Sakaguchi changed the way we view immunology. It demonstrated that protection and tolerance are two equally important aspects of immune system function. This provided science with a new understanding of how the body maintains balance between aggression against pathogens and “respect” for its own cells. This very idea became the foundation for the Nobel Assembly’s decision to award them the world’s highest honor in biomedical science in 2025.
— Could you explain how exactly this discovery changed our understanding of the immune system?
For decades, it was believed that the main “filter” for self-reactive lymphocytes operates during their maturation in the thymus. The Nobel trio showed that there is an additional, equally crucial “safety system” in the periphery, maintained by regulatory T cells. These cells monitor other immune cells and suppress dangerous reactions against the body’s own tissues. The FOXP3 gene turned out to be the “master regulator” of their development and function. Mutations in FOXP3 explain severe syndromes of uncontrolled autoimmunity in humans. This shifted the focus from central tolerance to the equally vital role of peripheral tolerance.
— What practical significance do these findings have for understanding autoimmune diseases?
Autoimmunity does not arise solely because some self-reactive clones “escaped” control in the thymus. Often, the peripheral inhibitory system breaks down. When regulatory T cells are quantitatively depleted or functionally defective, the immune system loses its “brakes” and begins to attack the body’s own organs. This framework gives clinicians a clear therapeutic target: we can either enhance regulatory T cells or restore their signaling pathways, thereby suppressing autoimmune inflammation. The scientific foundations for this approach are clearly described in the Nobel Committee’s materials and reviews in Nature.
— Are there already any clinical or experimental treatments based directly on this year’s Nobel discovery?
Yes. Trials are underway for cell therapies involving the transfer of regulatory T cells in autoimmune conditions and organ transplantation. Researchers are also testing drugs that can pharmacologically boost their number or activity. Both commercial and academic teams are building programs specifically based on knowledge about regulatory T cells and FOXP3. The list of such studies continues to grow through large-scale multicenter trials, though these methods have not yet become part of routine clinical practice.
— If we translate this discovery into the language of students and future doctors, what is the key lesson they should take away from this year’s Nobel Prize?
The immune system has not only a gas pedal but also a brake pedal. The success of treatment often depends on whether we can not only activate the immune response but also properly slow it down when necessary. Understanding regulatory T cells and the role of FOXP3 teaches us to think systemically — to search for defects in mechanisms of control and self-tolerance. This is directly relevant to autoimmunity, allotransplantation, and even oncology, where sometimes the opposite strategy — releasing the brakes — is required.
— What areas of immunological research are currently being developed at Karazin University?
Today, the Department of Infectious Diseases and Clinical Immunology at Karazin University is one of the most active research centers combining the classical traditions of the Kharkiv medical school with innovative approaches of modern biomedicine. Our work focuses on pressing issues of modern medicine, particularly the study of mechanisms of immune tolerance, development of autoimmune processes, post-infectious damage, and restoration of immune balance.
The department conducts studies that integrate classical immunology with modern experimental technologies. Researchers are exploring cell-free cryopreserved biological preparations derived from the placenta, spleen, and cell cultures. These preparations contain natural regulatory molecules capable of modulating the immune system, reducing inflammation, and promoting tissue repair. This opens new possibilities for creating safe and effective treatments for immune-related diseases.
A major focus is placed on translational research, which enables the transfer of experimental results into clinical practice. We study interactions between the immune system and various organs — the heart, liver, kidneys, and nervous system — to better understand the mechanisms of inflammatory and degenerative diseases and find ways to prevent them.
Today, the Department of Infectious Diseases and Clinical Immunology is a modern educational and scientific space, where the experience of senior scientists is combined with the fresh perspectives of young researchers. Its mission is to advance modern Ukrainian immunology, to train specialists capable of scientific thinking, clinical precision, and implementing innovation in practical medicine.
— Finally, what would you wish for young researchers who dream of contributing to medical science?
I would advise young researchers to hold on to three simple but crucial principles.
First, always start from a real clinical question. True science begins where there is a patient’s need, not just a researcher’s curiosity. If the thought process moves from a clinical case to a mechanism and then back to practice, the results will have real value and help in treatment.
Second, verify every fact at its primary source. Do not rely on summaries or others’ interpretations — scientific credibility is born from precision, honesty, and independent thinking.
And third — extremely important — develop universal skills. Every young scientist should master research design, statistical analysis, biomedical data handling, and the principles of open science and transparent reporting. These skills transcend any specific topic and make a researcher competitive in any environment.
In immunology, as in all biomedical science, success does not come to those who speak the loudest, but to those who can combine a well-designed experiment with accurate analysis and honest validation of results.
