🧬 2025 Nobel Prize in Medicine: The Discovery of Peripheral Immune Tolerance
- Jacky Gao
- Oct 6
- 3 min read
Date: October 6, 2025
Source: Nobel Assembly at the Karolinska Institute
Keywords: immune tolerance, Nobel Prize, FOXP3, regulatory T cells, autoimmune disease, immunotherapy
A Breakthrough in Understanding the Body’s “Self-Control System”
The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi
for their groundbreaking discoveries on peripheral immune tolerance — a mechanism that prevents our immune system from attacking our own tissues.
This research solved one of the most fundamental mysteries of immunology:
“How does the immune system stay powerful enough to destroy pathogens, yet smart enough to avoid destroying us?”
The Discovery: How the Body Learns to “Tolerate Itself”
Our immune system constantly patrols the body, identifying and neutralizing invaders like viruses or bacteria.
But sometimes, self-reactive immune cells escape the body’s internal screening system.
Earlier research had described central tolerance, a process in the thymus where T cells that attack the body’s own antigens are eliminated.
Yet even with this system, some potentially dangerous immune cells still slip through.
The missing link was found in the peripheral immune tolerance system,
where specialized immune cells—called regulatory T cells (T-regs)—act as peacekeepers.
The Scientists Behind the Discovery
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Shimon Sakaguchi
In 1995, Sakaguchi identified a small population of T cells capable of suppressing autoimmune responses.
He named them regulatory T cells (T-regs) and later discovered that these cells express the marker CD25 and rely on the transcription factor FOXP3 for their development and function.
His work provided the first concrete evidence that “immune suppression” was an active, regulated process—not merely a passive failure.
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Mary E. Brunkow & Fred Ramsdell
Working in parallel in the United States, Brunkow and Ramsdell studied a rare mutant mouse known as scurfy, which developed lethal autoimmune disease.
They identified the defective gene responsible—FOXP3—and showed that the same gene mutation in humans causes IPEX syndrome, a severe, early-onset autoimmune disorder.
Their work linked the molecular mechanism (FOXP3) with the cellular actors (T-regs), completing the picture of peripheral immune tolerance.
Why It Matters
The concept of immune tolerance reshaped modern medicine.
It explained not only how the body avoids attacking itself but also provided clues for treating diseases where this system breaks down.
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Autoimmune Diseases
Disruption of FOXP3 or T-reg function can lead to diseases such as Type 1 diabetes, lupus, multiple sclerosis, and rheumatoid arthritis.
Therapies that aim to enhance T-reg function are now being explored as next-generation immunomodulators.
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Organ Transplantation
Understanding peripheral tolerance has enabled progress toward “immune acceptance” — reducing the need for lifelong immunosuppressive drugs.
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Cancer Immunotherapy
Interestingly, tumors sometimes exploit this same tolerance pathway.
By recruiting T-regs to suppress immune attack, they create a “safe zone” against the body’s defenses.
This makes modulating T-regs a double-edged strategy: boosting them for autoimmune diseases, blocking them for cancer therapy.
The Frontier Ahead: From Discovery to Therapy
Despite enormous progress, manipulating immune tolerance remains one of the most delicate challenges in modern medicine.
Too much suppression can lead to infection or tumor growth; too little can trigger autoimmune reactions.
Recent research explores several promising directions:
Selective T-reg expansion therapies using low-dose IL-2
Gene therapy approaches targeting FOXP3 expression
Metabolic regulation of immune tolerance through amino acid or lipid pathways
Microbiome interaction studies, revealing how gut bacteria influence peripheral tolerance
Together, these advances point to a future where medicine doesn’t just fight disease—but teaches the immune system when to fight and when to stand down.
The Aset Nutrition Perspective
At Aset Nutrition, we view this year’s Nobel discovery as a profound reminder of the body’s internal intelligence.
The immune system is not a weapon—it’s a conversation between balance and defense.
While our work focuses on bioactive compounds, cellular metabolism, and longevity nutrition,
we share the same scientific vision:
to enhance the body’s innate self-regulation — not by force, but by harmony.
The concept of “tolerance” extends beyond immunology;
it is the foundation of cellular communication, energy balance, and systemic stability.
Just as immune tolerance keeps us from self-destruction, metabolic tolerance keeps our cells resilient under stress.
In the age of precision health, the next revolution may not be in killing pathogens or suppressing symptoms,
but in teaching our biology how to adapt.
Final Thought
The discovery of peripheral immune tolerance is more than a medical milestone —
it’s a philosophical one.
It shows that strength in biology, as in life, comes not from aggression but from control.
As Shimon Sakaguchi once said:
“The immune system’s greatest power is not in attack, but in restraint.”
At Aset Nutrition, we believe the same principle applies to health itself.
Balance is not the absence of action—it’s the mastery of timing.
