Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi were awarded the Nobel Prize in Physiology or Medicine 2025 for their groundbreaking discoveries concerning peripheral immune tolerance. Their work provided fundamental knowledge on how the body's powerful immune system is regulated and kept in check, preventing it from attacking the body’s own organs.
The laureates are credited with identifying the immune system's "security guards": regulatory T cells. These cells are crucial for peripheral immune tolerance as they prevent other T cells from mistakenly destroying the body's own tissue.
Shimon Sakaguchi swam against previous research trends and hypothesized that the immune system required a security guard to keep T cells in check. In 1995, he presented a new class of T cells, demonstrating that they were characterized by carrying both the CD4 and CD25 proteins on their surface.
Meanwhile, Mary Brunkow and Fred Ramsdell investigated the scurfy mouse strain, which suffered from severe autoimmune disease due to T cells attacking its tissues. They successfully identified the mutant gene responsible for the condition and named it Foxp3. Brunkow and Ramsdell further revealed that mutations in the FOXP3 gene cause the serious human autoimmune disease IPEX.
Researchers subsequently pieced the puzzle together, proving that the FOXP3 gene controls the development of regulatory T cells discovered by Sakaguchi.
The discovery of regulatory T cells has laid the foundation for a new field of research and spurred the development of potential new treatments. This includes strategies to treat autoimmune diseases (e.g., promoting more regulatory T cells using interleukin-2 or isolating and multiplying them) and approaches for more effective cancer treatments (e.g., dismantling the walls of regulatory T cells tumors use for protection
