Awarded to:
Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi
For: Discoveries revealing how the body restrains its immune defences to prevent attacking itself — unlocking key mechanisms of immune tolerance.
Context
The 2025 Nobel Prize in Physiology or Medicine was awarded to two Americans — Mary Brunkow and Fred Ramsdell, and one Japanese scientist — Shimon Sakaguchi, for their fundamental discoveries on regulatory T-cells (Tregs) and the FOXP3 gene, which explain how the immune system distinguishes self from non-self.
Their work demystified how the body avoids autoimmune reactions, laying the foundation for new therapies against autoimmune diseases, cancer, and transplant rejection.
Key Discoveries
- Shimon Sakaguchi’s Pioneering Work (1995)
- Discovered regulatory T-cells (Tregs) — a class of immune cells that suppress overactive immune responses.
- Demonstrated that without Tregs, the immune system attacks the body’s own tissues.
- His work shifted focus from “attacking invaders” to “restraining immunity”.
- FOXP3 Gene and the ‘Scurfy Mouse’
- Mary Brunkow and Fred Ramsdell studied a mutant strain of mice, nicknamed “scurfy mice”, which suffered from fatal autoimmune disease.
- They identified mutations in a gene called FOXP3 as the cause.
- This gene was later found to regulate Treg cell function — establishing genetic control over immune tolerance.
- Linking FOXP and Human Disease
- Mutations in FOXP3 cause IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) — a severe autoimmune disorder in infants.
- This discovery provided direct evidence that loss of immune restraint leads to autoimmunity.
Scientific and Medical Impact
- The discovery redefined immunology, introducing the concept of “peripheral immune tolerance” — the regulation of immunity outside the thymus.
- It provided the biological basis for treating autoimmune diseases, such as Type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.
- Helped improve organ transplantation outcomes by reducing immune rejection.
- Opened new research into Treg-based therapies for cancer and chronic inflammation.