Nobel 2025: Unlocking the Secrets of the Immune System

Context :

The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Frederick J. Ramsdell, and Shimon Sakaguchi for their pioneering work on peripheral immune tolerance, a process by which the immune system avoids attacking the body’s own tissues. Their discoveries have fundamentally advanced our understanding of immune regulation and have significant implications for treating autoimmune diseases, cancer, and transplantation outcomes.

About the Nobel Prize in Physiology or Medicine 2025

What it is:

The world’s most prestigious biomedical award, presented by the Nobel Assembly at Karolinska Institute, Sweden.
Winners receive a gold medal and prize money of approximately SEK 11 million.

2025 Laureates:

Shimon Sakaguchi – Osaka University, Japan
Mary E. Brunkow – Institute for Systems Biology, USA
Frederick J. Ramsdell – Sonoma Biotherapeutics, USA

Key Contributions

1. Regulatory T Cells (Tregs) and Peripheral Tolerance

Shimon Sakaguchi (1995) discovered regulatory T cells (Tregs), immune cells that act as the “police officers” of the immune system.
Function: Tregs prevent other immune cells from attacking the body’s healthy tissues.
Evidence: Removal of the thymus in newborn mice caused autoimmune diseases; reintroduction of normal T cells restored health, proving the existence of Tregs.

2. FOXP3 – The Master Control Gene of Tregs

Mary Brunkow and Frederick Ramsdell studied “scurfy” mice, which developed severe autoimmune diseases.
They discovered that a single defective gene, FOXP3, was responsible.
Role: FOXP3 acts as a switch converting normal T cells into regulatory T cells.
Clinical relevance: Without FOXP3, Tregs cannot form, leading to autoimmune conditions such as IPEX syndrome in humans.

3. Peripheral Immune Tolerance

The immune system has two levels of control:
- Central tolerance: Eliminates self-reactive immune cells in the thymus.
- Peripheral tolerance: Regulates immune cells throughout the rest of the body.
Tregs are central to peripheral tolerance, guarding tissues, preventing inflammation, and stopping uncontrolled immune responses.

Scientific and Clinical Significance

1. Cancer Therapy:

Many tumors recruit Tregs to evade immune detection.
Targeting or depleting Tregs can enhance anti-tumor immunity, improving outcomes of checkpoint inhibitors and CAR-T therapies.

2. Autoimmune Diseases:

Expanding or engineering Tregs (FOXP3+ Treg therapies) can calm pathogenic immunity in type 1 diabetes, IBD, MS, and lupus.

3. Transplantation & Immune Tolerance:

Treg-based approaches may reduce long-term immunosuppression, lowering risks of infections and drug toxicity after organ or cell transplants.

4. Diagnostics & Biomarkers:

FOXP3 and Treg signatures serve as biomarkers for disease stratification, therapy response prediction, and clinical trial design.

5. Risk Management:

Suppressing Tregs may trigger autoimmunity, while boosting them could increase infection or tumor escape risks.
Understanding Treg biology allows safe, precision-based therapeutic strategies.

Conclusion:

The 2025 Nobel Prize recognizes the critical role of regulatory T cells in maintaining immune balance. These discoveries provide a foundation for advanced therapies in cancer, autoimmune disorders, and transplantation, marking a significant leap in precision medicine and immunology.

Source : Hindustan Times