On October 6, 2025, the Nobel Assembly at Karolinska Institutet announced that the 2025 Nobel Prize in Physiology or Medicine has been awarded to three immunologists: Mary E. Brunkow and Fred Ramsdell from the United States, and Shimon Sakaguchi from Japan. The trio shares the prize of 11 million Swedish kronor (approximately $1 million USD) equally for their groundbreaking discoveries on “peripheral immune tolerance” – a mechanism that keeps the immune system from mistakenly attacking the body’s own healthy tissues, thereby preventing autoimmune diseases.
– – Mary E. Brunkow (born 1961) is a senior program manager at the Institute for Systems Biology in Seattle, Washington. She earned her Ph.D. from Princeton University and has focused on genetic research related to immune regulation.
– – Fred Ramsdell (born 1960) is a scientific advisor at Sonoma Biotherapeutics in San Francisco, California. He holds a Ph.D. from the University of California, Los Angeles (1987) and has worked extensively on T-cell biology.
– – Shimon Sakaguchi (born 1951) is a Distinguished Professor at the Immunology Frontier Research Center, Osaka University, Japan. He received his M.D. (1976) and Ph.D. (1983) from Kyoto University and is renowned for his work on T-cell suppression.
These researchers, working independently in the 1990s and early 2000s, challenged the long-held scientific consensus that immune tolerance (the ability to ignore self-tissues) occurred only in the thymus during T-cell development – a process known as “central tolerance.” Instead, their work revealed a critical “peripheral” layer of control in the rest of the body.
Their contributions center on regulatory T cells (Tregs), a subset of immune cells that act like vigilant “security guards,” patrolling the body to suppress overzealous immune responses against harmless or self-antigens. In essence, the laureates showed that without functional Tregs and *Foxp3*, the immune system loses its brakes, leading to chaos. This peripheral tolerance complements central mechanisms, creating a multi-layered defense.
This work has transformed immunology from a descriptive field into one ripe for therapeutic innovation. Autoimmune diseases affect over 50 million people in the U.S. alone, including rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and lupus – conditions where the immune system turns traitor. By elucidating Treg biology, the laureates enabled strategies to “retrain” the immune system:
Broader implications include the following:
– – Autoimmune Treatments: Drugs that boost Treg function (e.g., low-dose IL-2 therapies) are in trials to dampen inflammation without broad immunosuppression.
– – Cancer Immunotherapy: Tregs can sometimes shield tumors from attack; inhibiting them enhances checkpoint inhibitors like PD-1 blockers, improving outcomes in melanoma and lung cancer.
– – Organ Transplants: Treg infusions help prevent rejection by promoting tolerance to foreign tissues, reducing reliance on lifelong drugs.
Several therapies inspired by this research are now in advanced clinical trials, with real-world approvals on the horizon. As the Nobel Committee noted, these insights explain “why not all individuals develop serious autoimmune diseases despite genetic risks,” offering hope for personalized medicine. The announcement has sparked widespread excitement in the scientific community, with early reactions highlighting its potential to address unmet needs in chronic diseases.