Abstract
The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi "for their discoveries concerning peripheral immune tolerance". This award celebrates research into the mechanisms by which the adaptive immune system learns to tolerate self-antigens, preventing horror autotoxicus, or autoimmune disease. The identification of the regulatory T cell, a type of white blood cell with the capacity to impose self-tolerance on immune responses in the peripheral blood and tissues, required a combination of innovative immunology and genetics. The decades-long task of characterising this cell that can shut down autoimmunity finally intersected with the genetic mapping of the gene FOXP3, which underlies a rare autoimmune condition in humans and mice. This fusion of mouse models and patient-based genetic analysis set off an explosion of research into immune regulation, which is still redefining our knowledge of biology and medicine.