Mary E. BRUNKOW, Fred Ramsdell And Shimon Sakaguchi are the winners of the Nobel Prize for Medicine 2025 thanks to their discoveries on Peripheral immune tolerancethe mechanism that prevents the immune system from damaging our own body by fighting only external pathogens. The discoveries of the three scientists refer to 1995, 2001 and 2003 studies in which they defined the role of a particular type of immune cells, i T -regulatory lymphocytes or Treg. This discovery proved to be important in the development of therapies to combat immune diseases, rejection of organs for transplants and tumors.
As the immune system does not attack our own body: peripheral immune tolerance
The immune system has the task of recognizing and eliminating external pathogens such as viruses and bacteria. To do this, it produces a vast repertoire of specialized cells to recognize specific molecules, the antigens. These are divided into two main “teams”: the cells of theinnate immunitylike the phagocytes, which provide the first and immediate line of defense, and those of theadaptive immunitylike B lymphocytes (which produce antibodies) and T lymphocytes, which develop a targeted and lasting response.
Specifically, the T lymphocytes have “sensors” on their surface, i cell receptorswhich thanks to their particular shape manage to recognize what is foreign and dangerous from what is harmless. Once a suspect molecule has been stored, a series of signals that activate other cells that come into action killing the pathogen are triggered.
There are different types of T lymphocytes, each with a role specialized in the immune system, for example: cells T Helperwhich coordinate the immune response and cells T citotoxicwhich act as “killer” by directly eliminating infected or tumor cells.
However, these cells are not always able to recognize only the “enemies” of our body, in fact there are autoimmune diseases that occur when immune cells attack our same cells by recognizing the so -called antigens self. This is the case of pathologies such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes.
The complex mechanism that controls our body has methods to prevent these unwanted situations: the immune tolerance. It is a fundamental property of the immune system that develops on two levels, the central tolerance and the peripheral tolerance – Awarded with the Nobel.
- Central tolerance: it was the “dominant theory” in the 80s, according to which the T lymphocytes were “educated” in thymea gland placed in the chest, not to attack the cells of your body. However, it was already known that this process was not perfect and that some Self-founding T lymphocytes they could “escape” this check.
- Peripheral tolerance: control over “defective” cells does not end in thyme. There is a second level of security implemented by a third class of T cells, i T -regulatory lymphocytes O Treg who have the task of “suppressing” excessive immune responses, preventing autoimmune reactions.
Just the discoveries that allowed to understand the latter process were rewarded with the Nobel Prize for Medicine a Mary E. BRUNKOW, Fred Ramsdell And Shimon Sakaguchi.
Who are the three winners of the Nobel Prize for Medicine and what they discovered
Shimon Sakaguchi (1951), today an emeritus professor at the University of Osaka, in 1995 when it was thought that tolerance developed only in thyme, identified through tops experiments, a pop population (characterized by CD4 and CD25 proteins on the surface) capable of acting as “guardians”, keeping the immune system and protecting the body from autoimmunic diseases.
Despite the discovery, many researchers remained skeptical. The definitive evidence that would confirmed his theory would have come from the work of two other scientists, Mary Brukow – Born in 1961 and Senior Program Manager at the Institute for Systems Biology in Seattle – e Fred Ramsdell – born in 1960 currently scientific consultant for Sonoma Biotherapeutics – who were studying a strain of sick mice, “scurfy” mice in an American laboratory. The two researchers identified a mutation in the Foxp3 gene on chromosome x responsible for the disease. This gene was also defective in children with hypex syndrome, an autoimmune disease.
The union of discoveries made it possible to demonstrate that the gene Foxp3 It is precisely the switch that program the development and function of Re regulatory T cellsthus revealing the molecular mechanism at the basis of the body’s ability to tolerate itself.
As stated by Olle Kämpipresident of the Committee for the Nobel:
Their discoveries have been decisive to understand the functioning of the immune system and the reason why not everyone develops serious autoimmune diseases.
Applications and developments of the discovery is worth the Nobel Prize
The Nobel Prize for Medicine 2025 was awarded for discoveries that took place more than 20 years ago. Why has it passed a long time? The answer, as with every Nobel Prize, lies in the practical applications: only in recent years, the best understanding of the role of Re regulatory T cells It made it possible to think and develop new therapeutic strategies in medicine. In fact, concrete care prospects have been opened in areas such as autoimmune diseases, organ transplants and oncology.
Enhance the action Treg cells could be crucial to combat autoimmune diseases and to reduce the risk of rejection in transplants. In oncology, however, the strategy to be used is opposite, block the function Tregs that are used by cancer cells as defended by other immune cells.
