2025 Nobel Prize in Physiology or Medicine.

Laureates

Shimon Sakaguchi (Japan)

Mary E. Brunkow (USA)

Fred Ramsdell (USA)


They were awarded “for their discoveries concerning peripheral immune tolerance.”


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What they discovered

1. Regulatory T cells (“Tregs”)

Shimon Sakaguchi discovered a subset of T cells (immune cells) — called regulatory T cells — which act like a control or “brake” system in the immune system: making sure immune responses don’t get out of hand and start attacking the body’s own tissues.

These are different from the immune cells that fight infections; they help maintain balance.



2. FOXP3 gene and its role

Mary Brunkow and Fred Ramsdell uncovered the Foxp3 gene, initially by studying mice (including “scurfy” mice, which have a mutation that causes severe autoimmune issues).

They showed that Foxp3 is essential for the development and proper function of regulatory T cells. Mutations of the human version of this gene lead to serious autoimmune disorders (like IPEX syndrome).



3. Peripheral immune tolerance

Broadly, their work defines how the immune system’s “peripheral tolerance” works. While previous thinking emphasized “central tolerance” (mechanisms in the thymus during immune cell development), their work showed there are important control & tolerance systems outside the thymus — in the peripheral immune system — that are essential to preventing autoimmune disease.

This understanding explains why many people don’t develop autoimmune diseases despite exposure to microbes, self-antigens, etc.





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Implications / Importance

Understanding Autoimmune Diseases: Their discoveries help explain what goes wrong in conditions like Type 1 diabetes, rheumatoid arthritis, IPEX syndrome, etc. When regulatory T cells don’t work properly or Foxp3 is mutated, peripheral immune tolerance fails.

Transplantation: Better control of immune tolerance could mean fewer rejections of transplanted organs or tissues, by modulating how the immune system reacts to “foreign” tissue.

Cancer Therapy: Because immune activation can kill cancer cells, there is interest in “lifting” certain tolerances, or manipulating regulatory T cells, to allow stronger anti-cancer responses — but in a controlled way so autoimmunity doesn’t result.

Drug and clinical trial applications: Their findings are already being used in research and trials that try to harness regulatory T cells (or affect Foxp3) to treat diseases.