Nobel Prize in Medicine: The 2025 Nobel Prize in Physiology or Medicine has been jointly awarded to three scientists—Mary E. Brunkow (USA), Fred Ramsdell (USA), and Shimon Sakaguchi (Japan)—for their groundbreaking discoveries concerning peripheral immune tolerance.
Their work fundamentally revealed how the immune system is actively “kept in check” to prevent it from turning against the body’s own healthy tissues, a process essential for avoiding autoimmune diseases.
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Nobel Prize in Medicine Honors Trio for Discovery of New Immune System’s ‘Brake’
This Nobel-winning research uncovered the existence and mechanism of the immune system’s security guards: regulatory T cells (Tregs) and the master gene that controls them, laying the foundation for a new field of research with vast therapeutic potential.
The Laureates and Their Transformative Discoveries
1. Shimon Sakaguchi: Discovering the Immune System’s Peacekeepers
In 1995, Shimon Sakaguchi, working at Kyoto University, challenged the established dogma that the immune system achieved self-restraint only by eliminating self-reactive T cells in the thymus (a process called central tolerance).
He hypothesised that a separate mechanism must exist to control rogue immune cells that escape the thymus and circulate in the body, which he termed peripheral immune tolerance.
- Key Discovery: Sakaguchi identified a previously unknown class of T cells that actively suppressed or turned off immune responses. These were the first-ever identified regulatory T cells (Tregs), which he initially characterized by the presence of the CD25 protein on their surface.
- Significance: This discovery introduced the concept that immune restraint is not merely a passive failure to launch an attack, but an active, controlled process carried out by a dedicated cell population.
2. Mary E. Brunkow and Fred Ramsdell: Unmasking the Master Controller
Several years after Sakaguchi’s initial finding, American scientists Mary E. Brunkow and Fred Ramsdell, working together, were investigating the genetic basis for a severe autoimmune disease in mice, often referred to as “scurfy” mice due to their overactive immune system and skin inflammation.
- Key Discovery: In 2001, Brunkow and Ramsdell discovered that the condition was caused by a mutation in a previously unknown gene they named Foxp3 (Forkhead box P3). They subsequently showed that mutations in the same gene in humans caused IPEX syndrome (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked), a rare but devastating autoimmune disorder.
- Significance: Their finding pointed to Foxp3 as the crucial master switch for immune regulation, confirming that this gene was essential for preventing the immune system from attacking the body.
3. The Unification of Findings: Linking Gene to Cell
The final piece of the puzzle came from Sakaguchi’s lab in 2003, which conclusively connected the two threads of research.
- The Link: Sakaguchi demonstrated that the Foxp3 gene discovered by Brunkow and Ramsdell was the master regulator that controlled the development and function of the regulatory T cells (Tregs) he had identified years earlier.
- Conclusion: The trio’s combined work established that Tregs, controlled by the Foxp3 gene, act as the immune system’s “brakes” or “security guards,” monitoring other immune cells and shutting down potentially self-destructive immune responses.
Mary Brunkow, Fred Ramsdell & Shimon Sakaguchi Awarded 2025 Nobel Prize in Medicine
Impact on Medicine
The identification of regulatory T cells and their Foxp3 control mechanism is a paradigm shift in immunology. This knowledge has immediate and profound implications for medicine, steering research toward new therapies for a host of conditions:
- Autoimmune Diseases: By understanding how the “brakes” fail, researchers are developing treatments aimed at boosting the function or numbers of Tregs to suppress disorders like Type 1 diabetes, multiple sclerosis, and rheumatoid arthritis.
- Cancer Immunotherapy: Tregs can sometimes be a hindrance in cancer, as they suppress the T cells that would otherwise attack tumor cells. The discoveries provide a blueprint for developing new cancer immunotherapies that aim to disarm Tregs in the vicinity of a tumor, thereby unleashing the patient’s immune system to fight the cancer.
- Transplantation: Manipulating Tregs holds promise for promoting tolerance to transplanted organs, which could significantly reduce the need for lifelong, high-dose immunosuppressive drugs.
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