NOBEL MEDICINE PRIZE 2025
08.10.2025
NOBEL MEDICINE PRIZE 2025
Context
The 2025 Nobel Prize in Physiology or Medicine was awarded jointly to Mary E. Brunkow, Frederick J. Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries on peripheral immune tolerance — a process that enables the immune system to distinguish between harmful pathogens and the body’s own healthy tissues. Their pioneering work has transformed modern understanding of immunity, autoimmunity, and therapeutic interventions.
About the Nobel Prize in Medicine
The Nobel Prize in Physiology or Medicine is the world’s highest recognition for achievements in the life sciences. It is awarded annually by the Nobel Assembly at the Karolinska Institute, Sweden, and includes a gold medal and a prize amount of approximately SEK 11 million (about USD 1 million). The award honours discoveries that significantly advance human health and biological understanding.
The Laureates
- Shimon Sakaguchi – Osaka University, Japan
- Mary E. Brunkow – Institute for Systems Biology, USA
- Frederick J. Ramsdell – Sonoma Biotherapeutics, USA
Together, their independent yet interconnected research established how specific immune cells — known as Regulatory T Cells (Tregs) — maintain balance in the immune system, preventing self-destruction through autoimmunity.
Their Discoveries
1. Regulatory T Cells (Tregs) and Immune Balance
In 1995, Shimon Sakaguchi identified a unique class of immune cells called Regulatory T Cells (Tregs) — often described as the police force of the immune system.
- These cells suppress the activity of over-reactive immune cells that might otherwise attack the body’s own tissues.
- Experiments showed that when the thymus (an immune organ) was removed from baby mice, they developed autoimmune diseases.
- However, when normal T cells were reintroduced, the mice recovered — confirming the presence of a distinct subset of protective immune cells.
This discovery provided the first evidence that immune self-tolerance is not solely established during development (in the thymus), but also actively maintained throughout life by specialized cells.
2. FOXP3 — The Master Gene of Tregs
In the early 2000s, Mary Brunkow and Frederick Ramsdell discovered the FOXP3 gene, which acts as the master switch controlling the formation and function of Tregs.
- Their research on mutant “scurfy” mice — which suffered from severe autoimmune disorders — revealed that a defect in the FOXP3 gene caused uncontrolled immune activation.
- Similarly, in humans, mutations in FOXP3 were linked to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked), a rare but fatal autoimmune disease.
- FOXP3 thus emerged as the critical transcription factor that turns ordinary T cells into regulatory guardians.
This discovery connected the dots between genetics, immune regulation, and clinical autoimmune disorders, opening a new frontier in precision immunology.
3. Peripheral Immune Tolerance
The immune system maintains two lines of defense and control:
- Central Tolerance – established in the thymus, where self-reactive immune cells are eliminated during development.
- Peripheral Tolerance – maintained in the body’s tissues, where Tregs actively prevent the activation of rogue immune responses.
Tregs are the core enforcers of peripheral tolerance, continuously patrolling the body to prevent unnecessary inflammation, maintain immune balance, and ensure that the immune system does not turn against self-tissues.
Scientific and Clinical Significance
The discoveries of Sakaguchi, Brunkow, and Ramsdell have reshaped medicine, offering new ways to modulate the immune system across multiple diseases.
- Many tumors recruit Tregs to shield themselves from immune attack.
- By targeting or depleting Tregs in the tumor microenvironment, researchers can boost the body’s natural anti-cancer responses.
- Such strategies enhance the effectiveness of checkpoint inhibitors and CAR-T cell therapies.
- Expanding or engineering FOXP3+ Tregs offers a precise way to calm immune hyperactivity in conditions like Type 1 diabetes, Multiple Sclerosis, Inflammatory Bowel Disease (IBD), and Lupus.
- Clinical trials are exploring Treg cell therapy as a next-generation treatment to restore immune harmony without broad immunosuppression.
3. Transplantation and Organ Tolerance
- Treg-based therapies may reduce the need for lifelong immunosuppressive drugs after organ or stem cell transplants.
- This could lower infection risks, improve quality of life, and enhance graft survival.
- FOXP3 expression and Treg-related molecular signatures serve as biomarkers for disease classification and therapy response prediction.
- These insights guide personalized immunotherapy and help in designing clinical trials.
Ethical and Clinical Balance
While the manipulation of Tregs holds great promise, it also requires careful balance:
- Inhibiting Tregs too aggressively may trigger autoimmune reactions.
- Enhancing Tregs excessively could lead to immune suppression, making patients vulnerable to infections or allowing tumors to escape immune detection.
Thus, the challenge for medicine lies in achieving precision regulation — strengthening or softening the immune system only as needed, and under close monitoring.
Broader Impact on Global Health
The 2025 Nobel Prize highlights how fundamental immunological discoveries can drive clinical revolutions. The identification of Tregs and FOXP3 has inspired new fields such as:
- Cellular immunotherapy
- Gene editing for immune modulation
- Personalized immune diagnostics
These advancements have shifted medicine toward targeted, patient-centric care, blending laboratory insights with therapeutic innovation.
Conclusion
The 2025 Nobel Prize in Medicine celebrates a profound leap in understanding the immune system’s internal balance. Through the discoveries of Sakaguchi, Brunkow, and Ramsdell, science has uncovered how the body’s defense forces also practice restraint — a vital principle for survival. Their work continues to guide the development of precision immunotherapies that promise safer treatments for cancer, autoimmune diseases, and organ transplants.
Ultimately, this year’s Nobel recognition underscores a timeless truth in biology — that the strength of life lies not only in defense, but in harmony.