Three researchers have revealed how regulatory T cells and the FOXP3 gene protect the body from autoimmune diseases and lay the foundation for new treatments for cancer and transplantation.
Three researchers – Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi – have won the 2025 Nobel Prize in Physiology or Medicine for a discovery that changed our understanding of the immune system. They revealed how the body protects itself from self-attack using “regulatory T cells” – internal gatekeepers that regulate the strength of the immune response and maintain a delicate balance between protecting against invaders and preventing autoimmune diseases.
Why does the immune system need restraint?
The immune system is a sophisticated mechanism that protects us every day from viruses, bacteria, and other microbes. It can recognize foreign invaders, but it can sometimes confuse them with the body's own cells and tissues. Such a mistake leads to autoimmune diseases – conditions in which the immune system attacks the pancreas, joints, or skin, for example.
Until the 1990s, scientists believed that the system protected us primarily through a "central selection" mechanism in the thymus - an organ where T cells that might recognize the body as foreign are destroyed. However, it turned out that this mechanism is not enough: dangerous T cells sometimes manage to "escape" and cause disease. This is where the research of the laureates comes into play.
Discovery of the brake cells – regulatory T cells
In Japan, Sakaguchi studied mice without a thymus and showed that the absence of this organ caused a severe outbreak of autoimmune diseases. His experiments led him to realize that there was a special population of T cells that prevented an overreaction – cells he called regulatory T cellsThey carry unique proteins on their surface (CD4 and CD25) and their role is to "cool down" the immune system when there is a risk of self-attack.
At the same time, in the US, Bronkow and Ramsdell were working at a biotech company in Washington and studying "scurfy" mice – a strange strain that had been created in the 1940s as part of the Manhattan Project's radiation experiments. These mice developed scaly skin, enlarged lymph nodes and severe infections. After years of careful mapping, they identified the mutation that caused this: a defect in a new gene, FOXP3.
It soon became clear that similar mutations in FOXP3 also cause a rare but fatal disease in humans – IPEX – in which the immune system goes berserk and attacks the body. From there, the path to understanding was short: FOXP3 is the gene that enables the existence and function of the regulatory T cells discovered in Japan.
What is the medical significance?
These discoveries created a new field of research: Peripheral immune toleranceClinical trials are currently underway in which:
- Attempts are being made to suppress regulatory T cells in the vicinity of cancerous tumors to allow the immune system to attack the cancer.
- Increasing the number of regulatory T cells in patients with juvenile diabetes or other autoimmune diseases, for example by administering interleukin-2.
- Regulatory T cells that have been processed in the laboratory are returned to the body to prevent transplant rejection.
Understanding how the body maintains a delicate immune balance opens doors to the development of new drugs – from preventing complications after transplants to treating cancer and autoimmune diseases.
The three winners
Mary E. Bronkow – Born in 1961, received a doctorate from Princeton University, currently a senior director at the Institute for Systems Biology in Seattle.
Fred Ramsdell – Born in 1960, received a doctorate from the University of California, Los Angeles, currently a scientific consultant at Sonoma Polytechnics in San Francisco.
Shimon Sakaguchi – Born in 1951, received a Doctor of Medicine and PhD from Kyoto University, currently a senior professor at Osaka University.
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