The 2025 Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Dr. Shimon Sakaguchi for discoveries that revealed how the immune system applies “brakes” to stop itself from attacking the body. Their work established the biology of regulatory T cells (T-regs) and the master gene FOXP3, transforming understanding of autoimmune disease, transplantation tolerance, and even cancer immunotherapy.
What they discovered
In the mid-1990s, Shimon Sakaguchi identified a subset of T cells marked by CD25 that could suppress harmful immune responses, overturning the then-dominant idea that self-reactive cells were eliminated only in the thymus (“central tolerance”). He showed these T-regs are essential to peripheral tolerance—the second line of control that prevents friendly fire once T cells circulate in the body.
In 2001, Mary Brunkow (first author on seminal mouse genetics work) and Fred Ramsdell connected devastating autoimmune syndromes to mutations in the FOXP3 gene—explaining the “scurfy” mouse phenotype and its human counterpart, IPEX syndrome. Subsequent studies showed FOXP3 programs the identity and function of T-regs, providing the molecular handle to find, track, and ultimately engineer these cells.
Why it matters
Together, these insights mapped a control circuit that keeps immunity in balance—strong against pathogens, restrained against self. Clinically, that balance is the difference between health and autoimmune disease; between rejecting and accepting a transplanted organ; and, conversely, between a tumor escaping immune attack and one that can be recognized and destroyed. Their discoveries seeded hundreds of clinical trials that modulate T-regs (expanding or engineering them for autoimmunity and transplantation; dialing them down to boost anti-tumor responses). Companies such as Sonoma Biotherapeutics and Quell Therapeutics are advancing T-reg therapies inspired by this work.
The laureates
Mary E. Brunkow is affiliated with the Institute for Systems Biology (ISB), Seattle. Her mouse genetics and human immunology work were pivotal in nailing FOXP3 as the master regulator of T-regs.
Fred Ramsdell, a UCLA alumnus and co-founder of Sonoma Biotherapeutics, helped define FOXP3 biology across mouse and human systems and later translated T-reg science toward therapies. (In a lighter note, news reports joked the Nobel committee initially struggled to reach him while he was hiking off-grid.)
Shimon Sakaguchi, a Japanese immunologist, is widely credited with the modern discovery of T-regs and with demonstrating their essential role in maintaining self-tolerance and preventing autoimmunity.
The prize and the moment
The Nobel Assembly at Karolinska Institutet credited the trio for “groundbreaking discoveries concerning peripheral immune tolerance,” awarding them 11 million Swedish kronor (about $1.1 million). As is tradition, the medicine prize kicked off Nobel week; medals and diplomas will be presented at the December 10 ceremonies in Stockholm.
What comes next
Basic biology has already become medical possibility. With a genetic switch (FOXP3) to define and stabilize T-regs and decades of mechanistic insight into how these cells police the immune response, researchers are moving from “can we control T-regs?” to “how precisely and for whom?”. Expect to see continued progress in ex vivo T-reg expansion for type 1 diabetes, inflammatory bowel disease, and transplant tolerance, alongside careful trials that pair T-reg modulation with checkpoint inhibitors in oncology to fine-tune anti-tumor immunity without triggering autoimmunity. Reviews and expert commentary hail the award as overdue recognition for a discovery that reframed immunology’s central question—from “how do we turn immunity on?” to “how do we keep it in tune?”.
