Why in News
- The 2025 Nobel Prize in Physiology or Medicine was awarded to Shimon Sakaguchi (Japan), Mary Brunkow, and Fred Ramsdell (USA).
- Recognition is for discoveries related to the human immune system, particularly regulatory T cells (Tregs) and peripheral immune tolerance.
- Significance: Findings have paved the way for novel therapies in cancer, autoimmune diseases, and organ transplantation.
Relevance
- GS-3 (Science & Technology):
- Advances in immunology and biotechnology
- Implications for healthcare, personalized medicine, and public health
- GS-2/3 (Ethics & Innovation):
- Research ethics, translational research, and equitable access to advanced therapies

Human Immune System
- Components:
- B cells: Produce antibodies to neutralize pathogens.
- T cells: Mediate cellular immunity; can kill infected cells or regulate immune response.
- Neutrophils & Macrophages: Innate immune cells; engulf pathogens.
- Function: Identify and eliminate foreign antigens while maintaining tolerance to self-cells.
- Tolerance: Prevents immune system from attacking body’s own tissues. Two types:
- Central tolerance: Elimination of self-reactive T cells in thymus.
- Peripheral tolerance: Mechanisms outside the thymus, ensuring immune cells do not attack self-cells in circulation.
Key Discoveries by the Laureates
- Shimon Sakaguchi (1995):
- Identified a previously unknown class of regulatory T cells (Tregs) in mice.
- Showed these cells suppress autoimmunity by controlling other T cells.
- Introduced the concept of peripheral immune tolerance beyond central tolerance.
- Mary Brunkow & Fred Ramsdell (2001):
- Discovered that mutations in the Foxp3 gene cause severe autoimmune disease (IPEX syndrome) in humans.
- Demonstrated the mechanistic link between Foxp3 and Tregs, establishing Tregs as the immune system’s “security guards.”
Mechanism of Peripheral Immune Tolerance
- Regulatory T Cells (Tregs):
- Express Foxp3 gene.
- Monitor and regulate other immune cells to prevent self-reactivity.
- Deficiency or mutation leads to autoimmune disorders, where the body attacks its own tissues.
- Impact on Disease:
- Cancer: Manipulating Tregs can boost anti-tumor immunity.
- Autoimmune Diseases: Treg-targeted therapies reduce abnormal immune attacks (e.g., Type 1 diabetes, IPEX).
- Transplantation: Enhances graft acceptance by controlling immune rejection.
Clinical & Research Significance
- Peripheral Tolerance: Launched a new field of research.
- Medical Applications:
- Novel immunotherapies for cancer (checkpoint inhibitors, CAR-T).
- Treatments for autoimmune diseases (immune modulation via Tregs).
- Organ transplantation: Reduces rejection risk.
- Ongoing Research: Several therapies targeting Tregs are in clinical trials.
Broader Scientific Context
- Previously, immune tolerance was thought to occur only through central tolerance (elimination in thymus).
- Discoveries reveal multi-layered immune regulation, highlighting:
- Complexity of immune system
- Need for balance between immunity against pathogens and self-tolerance
- Showcases how basic research can translate into therapeutic breakthroughs.
Numbers & Facts
- Foxp3 mutations: Cause IPEX syndrome, a rare but life-threatening autoimmune disorder.
- Treg discovery timeline:
- 1995: Sakaguchi identifies Tregs in mice
- 2001: Brunkow & Ramsdell link Foxp3 mutations to autoimmune disease
- Clinical trials: Multiple Treg-based therapies underway globally for autoimmunity, cancer, and transplantation.