The Nobel Prize in Physiology or Medicine this year has been awarded to Mary E. Brunkow (Institute for Systems Biology, Seattle), Frederick J. Ramsdell (Sonoma Biotherapeutics, San Francisco) and Shimon Sakaguchi (Osaka University) “for their discoveries concerning peripheral immune tolerance.” The 11 million Swedish kronor prize will be shared equally, and the award ceremony will traditionally take place on 10 December in Stockholm.
The prize recognizes not a specific molecule but a mechanism that shapes approaches to drug development. FOXP3⁺ regulatory T cells are a controllable axis: their expansion or stabilization helps restrain autoimmune responses and graft rejection. Reducing their numbers or suppressing their function can enhance anti-tumor immunity.
More than 200 clinical trials are probing this lever across asthma, inflammatory bowel disease, dermatology, transplantation, and oncology — indicating a broad, partnerable translational pipeline.
The story of the discovery is as follows:
In 1995, Sakaguchi described a special subclass of T lymphocytes, CD4+CD25+ — regulatory T cells (Treg), which curb autoimmune aggression.
In 2001, Brunkow and Ramsdell identified in so-called “scurfy” mice a mutation in the Foxp3 gene and linked FOXP3 mutations in humans to the severe IPEX syndrome.
By 2003, it had become clear that FOXP3 governs the development of Treg.
These studies laid the foundation for a new field and spurred the creation of therapies in which Treg activity is boosted in autoimmune diseases and after transplantation or, conversely, dampened in cancer treatment; several approaches are already being tested in clinical trials.
Briefly about the laureates.
Mary E. Brunkow — molecular biologist, at the time of the award — Institute for Systems Biology; co-author of the key work linking a Foxp3 mutation to immune dysregulation.
Frederick J. Ramsdell — immunologist, scientific advisor at Sonoma Biotherapeutics; co-author of the Foxp3 and IPEX investigations.
Shimon Sakaguchi — immunologist, Distinguished Professor at Osaka University; first to describe regulatory T cells as guardians of peripheral tolerance.
For the record, in 2024 the Nobel Prize was awarded to Victor Ambros and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation.” And in 2023 the prize went to Katalin Kariko and Drew Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.”