This year's Nobel Prize in physiology or medicine went to three scientists who discovered "peripheral immune tolerance." They studied how the immune system avoids harming the human body through the principles of peripheral immune tolerance and the role of regulatory T cells (immune cells). Their research is credited with opening new avenues for treating autoimmune diseases and cancer.
The Nobel Committee at Sweden's Karolinska Institute announced on the 6th (local time) that it selected Mary Brunkow (64), senior program manager at the Institute for Systems Biology in the United States; Fred Ramsdell (65), advisor at Sonoma Biotherapeutics in the United States; and Shimon Sakaguchi (74), distinguished professor at Osaka University in Japan, as the winners of the Nobel Prize in physiology or medicine.
◇ An immune strategy that prevents friendly fire
Immune cells detect the surface proteins of external invaders such as viruses or bacteria as antigens and bind antibodies to eliminate them. The immune system protects the body through this antigen-antibody reaction. The problem is that, in this process, normal cells can be mistaken for invaders. Autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, Crohn's disease, and lupus occur this way.
Immune tolerance is a method to prevent the immune cells, the army that protects the body, from mistakenly striking friendly, normal cells. It ensures that the immune system does not respond to self antigens, which are proteins of the body's own cells. In other words, immune tolerance can be called "accurately recognizing our side so the immune system does not attack."
Immune tolerance can be divided into central immune tolerance and peripheral immune tolerance. T cells, immune cells that detect antigens and attack, form central immune tolerance in the thymus, and B cells, which produce antibodies, form it in the bone marrow. T cells or B cells that react to self antigens are eliminated in this process or differentiate into regulatory T cells. Alternatively, B cells are altered so they do not respond to self antigens.
◇ Shimon Sakaguchi discovers regulatory T cells
Professor Sakaguchi was recognized for discovering regulatory T cells, the key to peripheral immune tolerance. In 1995, in the international journal The Journal of Immunology, Sakaguchi proved that the T cell surface that calms the immune system bears not only the CD4 protein but also a protein called CD25. These T cells are regulatory T cells.
Peripheral immune tolerance is the process of finishing the task that central immune tolerance does not fully complete. Some immune cells may bind to self antigens but fail to be eliminated and move to peripheral sites in the body. Peripheral immune tolerance emerges to remove these, occurring mainly in secondary lymphoid organs. Regulatory T cells are the most actively involved in this process.
Regulatory T cells detect when other immune cells have bound to proteins of normal human cells and calm those immune cells. In other words, they detect comrades who have mistaken friends for foes and prevent friendly fire.
◇ Gene mutations regulate regulatory T cells… opening horizons for new therapies
Senior manager Brunkow and advisor Ramsdell identified the extent of regulatory T cell development, which aligns with Professor Sakaguchi's research. While working at the same biotech company in 2001, they published in Nature Genetics mouse experiment results showing that mutations in a gene called "Foxp3" increase susceptibility to autoimmune diseases. They also found that, in humans, mutations in the Foxp3 gene can cause IPEX syndrome.
Sakaguchi later proved that Foxp3 regulates the development of regulatory T cells. With this research, the study of peripheral immune tolerance via regulatory T cells, the achievement of the three scientists, was completed. It was later revealed that tumors can recruit regulatory T cells to protect themselves from the immune system, and research has proceeded to remove the regulatory T cell barrier so the immune system can access tumors. In autoimmune diseases, research is under way to promote the generation of regulatory T cells.
The Nobel Committee said, "The laureates discovered regulatory T cells, guardians of the immune system, laying the foundation for a new field of research," adding, "Through this, we hope to treat autoimmune diseases, provide more effective cancer therapies, and prevent severe complications after stem cell transplantation."
It added, "There are far more cases in which researchers are testing ways to harness regulatory T cells to fight disease," and stressed, "Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi have provided fundamental knowledge about how the immune system is regulated and maintained through their groundbreaking discoveries."
References
Science (2003), DOI: https://doi.org/10.1126/science.1079490
Nature Genetics (2001), DOI: https://doi.org/10.1038/83784
Nature Genetics (2001), DOI: https://doi.org/10.1038/83707
The Journal of Immunology (1995), DOI: https://doi.org/10.4049/jimmunol.1100364