In October of 2025, the Nobel Prize in Physiology or Medicine was awarded to three scientists who figured out how the immune system hits the brakes before it accidentally destroys us. That vital work is now reshaping treatment for autoimmune disease, cancer, and even organ transplants.
The 2025 prize went to Shimon Sakaguchi, Mary E. Brunkow, and Fred Ramsdell for uncovering a powerful self‑control system called “peripheral immune tolerance.” In simple terms, they showed how special cells and a single key gene team up to stop the immune system from attacking your own tissues.
In the 1990s, Sakaguchi discovered a mysterious subtype of T cells that didn’t start fights; they stopped them. These are now famous as regulatory T cells, or T‑regs. A few years later, working with “scurfy” mice that died young from raging inflammation, Brunkow and Ramsdell traced the problem to a single gene called FOXP3, which turned out to be the master switch for those calming T‑regs.
Your immune system is built for a constant tightrope walk: react hard and fast to viruses and bacteria, but ignore your own cells and harmless stuff like pollen or food proteins. When that balance fails, you get autoimmune diseases such as type 1 diabetes, lupus, and rheumatoid arthritis, or you reject a transplanted organ.
For a long time, textbooks focused on 'central tolerance,' which happens in the thymus and bone marrow, where self-reactive immune cells are removed before they enter the body. Sakaguchi’s research added another important layer: peripheral tolerance. Here, T‑regs move through the body and stop immune responses that escaped the first check.
Those sickly scurfy mice that Brunkow and Ramsdell studied looked like an immune system horror story with flaky skin, huge lymph nodes, massive inflammation, and early death. When the team zeroed in on the cause, they found a mutation in FOXP3, a gene that acts as a master regulator for regulatory T cells.
When FOXP3 is disrupted, T‑regs never properly develop, leaving the immune system with no brakes. Similar FOXP3 mutations in humans cause a rare but devastating autoimmune syndrome (often called IPEX), giving strong genetic proof that this pathway is essential for immune self‑control.
Follow‑up studies confirmed that FOXP3 is highly expressed in T‑regs and that turning this gene on helps create and stabilize these cells, while losing it wipes out their suppressive power. That one discovery turned a confusing cluster of autoimmune problems into a coherent story: a faulty FOXP3 gene leads to too few T‑regs, which leaves the immune system free to attack the body’s own tissues.
What sounds like deep, basic immunology is now pushing real therapies forward. The Nobel committee highlighted that more than 200 clinical trials are underway to harness T‑regs and FOXP3‑driven pathways in humans.
Researchers are now looking at several approaches:
-
They are trying to boost or increase T‑regs to reduce autoimmune diseases and help transplanted organs last longer without strong, broad immunosuppressive drugs.
-
They are also testing ways to adjust or temporarily lower T‑regs in cancer, since too much self-tolerance can let tumors avoid the immune system.
This research builds on earlier Nobel Prize-winning discoveries about immune 'checkpoints' such as CTLA‑4 and PD‑1, which led to modern cancer immunotherapy. These treatments use drugs to remove the immune system’s brakes and help it attack tumors. While checkpoint therapy removes certain brakes to fight cancer, T‑regs and FOXP3 offer a way to slow the immune system down when it is causing too much harm.
Why is this important?
At first, 'peripheral immune tolerance' may sound technical or specialized. In fact, it relates to some of the biggest issues in medicine today. Autoimmune diseases are becoming more common, organ transplants are increasing, and cancer is still a major cause of death. All of these involve how the immune system is controlled.
By explaining how the immune system controls itself through regulatory T cells and the FOXP3 gene, this year’s winners made it possible to develop new treatments that adjust the immune system’s behavior instead of just using strong drugs like steroids. This approach allows for much better control of the immune system.
Sources:
https://www.nobelprize.org/prizes/medicine/2025/summary/
https://isbscience.org/news/our-people/the-science-behind-the-nobel-prize/
https://www.autoimmuneinstitute.org/resources/autoimmune-diseases-list/
https://www.chop.edu/conditions-diseases/ipex-syndrome
https://pmc.ncbi.nlm.nih.gov/articles/PMC6303476/
