The Immune System's Guardians: Trio Wins 2025 Nobel Prize in Medicine

The Nobel Assembly at the Karolinska Institute in Sweden has awarded the 2025 Nobel Prize in Physiology or Medicine to three scientists for their groundbreaking work in understanding the immune system. Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi were honored for "their discoveries concerning peripheral immune tolerance" .

This crucial mechanism prevents our powerful immune system from turning against the body's own tissues, a breakdown that leads to autoimmune diseases. The laureates identified and characterized "regulatory T cells," which act as the immune system's security guards . Their work has not only reshaped modern immunology but also paved the way for revolutionary new treatments for a range of medical conditions.

The Laureates and Their Breakthrough

The following table introduces the three Nobel laureates and summarizes their key contributions to this collective discovery :

| Shimon Sakaguchi |

Osaka University, Japan , Provided the foundational discovery in 1995 by identifying a specific class of cells, regulatory T cells, that prevent autoimmune attacks . |

| Mary E. Brunkow |

Institute for Systems Biology, USA , Co-discovered the Foxp3 gene in 2001, linking its mutations to severe autoimmune disorders and establishing its role in controlling regulatory T cells . |

| Fred Ramsdell |

Sonoma Biotherapeutics, USA , Co-discovered the Foxp3 gene, revealing how this "master regulator" governs the development and function of the regulatory T cells identified by Sakaguchi . |

A Delicate Balance: How the Body Tames Its Own Defenses

For the body to stay healthy, the immune system must perform a delicate balancing act. It needs to be aggressive enough to fight off viruses, bacteria, and other pathogens, but it must also be able to recognize the body's own cells to avoid attacking them. The concept of "immune tolerance" is the principle that prevents this self-attack .

Before the work of this year's laureates, scientists understood that the body eliminated many self-reacting immune cells in the thymus, an process known as "central tolerance" . However, it was clear that this alone could not explain the full picture of self-tolerance.

Shimon Sakaguchi's research was pivotal in filling this gap. His work in the 1990s demonstrated that a separate, active mechanism exists outside the thymus to keep the immune system in check. He identified a specific type of white blood cell, the regulatory T cell (often called a "T-reg"), that functions as a peacekeeper, monitoring other immune cells and suppressing those that might target the body's own organs .

The Genetic Key: Unlocking the Mystery of Autoimmunity

The discovery of regulatory T cells opened a new field of research, but a critical question remained: what controls these cells? The answer came through the collaborative work of Brunkow and Ramsdell. In 2001, they uncovered the role of a gene called Foxp3 .

Their research showed that the Foxp3 gene is the master switch responsible for the proper development and function of regulatory T cells. Mutations in this gene lead to a catastrophic failure of immune control, resulting in severe autoimmune conditions in both mice and humans, such as IPEX syndrome . Sakaguchi later integrated these findings, confirming that Foxp3 is the key regulator operating within the very cells he had discovered .

This connection provided the definitive molecular evidence that solidified the importance of regulatory T cells in maintaining health.

A Foundation for the Medicine of Tomorrow

The discoveries of Brunkow, Ramsdell, and Sakaguchi have provided a new framework for understanding, treating, and potentially curing a wide array of diseases. By understanding how the immune system is naturally suppressed, scientists can now develop strategies to manipulate this system for therapeutic benefit .

In autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, the goal is to boost the function of regulatory T cells to calm the inappropriate immune attack on the body . Conversely, in cancer, tumors can sometimes exploit these same mechanisms to hide from the immune system. New immunotherapies aim to temporarily dampen regulatory T cell activity in the tumor environment, thereby "releasing the brakes" on the immune system and allowing it to fight the cancer more effectively .

According to the Nobel Assembly, these discoveries have "laid the foundation for a new field of research" and "spurred the development of new treatments," several of which are already being evaluated in clinical trials . The work of these three scientists stands as a testament to how unraveling a fundamental biological mystery can open the door to healing millions.