This week, the three winners of the 2025 Nobel Prize in Physiology or Medicine were announced, who discovered the function of regulatory T cells and the FoxP3 gene. Today, thanks to their findings, advances are being made in the field of immunology. Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi were this year’s winners thanks to their discoveries regarding peripheral immune tolerance. In 1995, Shimon Sakaguchi demonstrated that the immune system was more complex than previously believed, discovering a new type of cell, the regulatory T cell. In 2001, Mary E. Brunkow and Fred Ramsdell made another breakthrough by discovering a mutation in the FoxP3 gene in mice with autoimmune diseases. This showed that mutations in this gene in humans cause serious autoimmune diseases such as IPEX, which affects children and causes symptoms such as diarrhea, diabetes, and eczema due to a defective gene on the X chromosome.
Dr. Shimon Sacaguchi discovered which cells slow down the immune system. The immune system is capable of defending us from all external aggressors without damaging our own organs or tissues. Mary Brunkow and Fred Ramsdell discovered the master gene that controls this process. This is like the master key that controls autoimmunity, and that is a process of basic immunology with enormous clinical implications,” explains Dr. Fernando Figueroa, rheumatologist and Principal Investigator at the IMPACT Center at the University of the Andes.
Why is this finding important?
Our immune system is responsible for defending our body against external agents such as viruses, bacteria, and other pathogens by detecting them as threats and differentiating between what is internal and what is external. This function is made possible by regulatory T cells, which prevent immune cells from attacking the body’s own cells. However, when this does not occur, autoimmune diseases develop.
“As a clinical problem, autoimmunity affects no less than 5% of the world’s population. And a percentage, almost 20% of those people, have not only one but two autoimmune diseases, and some of them have three or more, highlighting the importance of the genes that control it,” explains Dr. Fernando Figueroa.
Our research
In a study published in 2020 by EMBO Reports, it was discovered that mesenchymal stem cells, which are used at the IMPACT Center, transfer their mitochondria to a type of immune cell called CD4+ T cells. Upon receiving these mitochondria, the cells transform into regulatory T cells, putting the brakes on the immune system. Furthermore, it was shown that this process not only enhances the FoxP3 gene, but also restricts the inflammation caused by autoimmune diseases. This revelation is fundamental: immune tolerance is not only genetic programming, but also metabolic communication, suggesting that cellular fate is metabolically negotiable, not genetically predetermined.
“Autoimmunity is no longer just a problem of defective genes. It is a problem of cellular communication that can be restored by adding mitochondria. It’s like putting new engines in a boat to get it running powerfully again,” said Maroun Khoury, executive director of the IMPACT Center.