The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries in peripheral immune tolerance—a mechanism that prevents the immune system from attacking the body’s own tissues. Their work has transformed our understanding of immune regulation, paving the way for innovative treatments for autoimmune diseases, cancer, and improving organ transplant success rates.
What they won the Nobel Prize for
The trio was recognized for uncovering the pivotal role of regulatory T cells (T-regs) in maintaining immune balance outside the thymus. For decades, central tolerance, which means the elimination of self-reactive immune cells in the thymus, was considered the primary defense against autoimmunity. Sakaguchi’s 1995 work identified T-regs, specialised immune cells that suppress overactive immune responses, establishing that self-tolerance is actively maintained in peripheral tissues.Brunkow and Ramsdell’s research on the “scurfy” mouse strain revealed that mutations in the FOXP3 gene disrupt regulatory T cell function, leading to fatal autoimmune disorders. Their findings linked these genetic insights to the human autoimmune disorder IPEX syndrome, demonstrating how FOXP3 mutations cause catastrophic immune dysfunction. Collectively, their discoveries have opened new avenues for therapies targeting autoimmune diseases, cancer, and transplant rejection.
Mary E. Brunkow
Mary Brunkow earned her Ph.D. from Princeton University and currently serves as a Senior Program Manager at the Institute for Systems Biology in Seattle. Her work focused on identifying the FOXP3 gene mutation in scurfy mice, establishing the molecular basis of regulatory T cell function and connecting it to human immune diseases. Brunkow’s research has been central to understanding how T-regs prevent autoimmunity and maintain immune system balance.
Fred Ramsdell
Fred Ramsdell received his Ph.D. from the University of California, Los Angeles (UCLA) and is a Scientific Advisor at Sonoma Biotherapeutics in San Francisco. Collaborating closely with Brunkow, Ramsdell helped identify the FOXP3 gene mutation and demonstrated its critical role in immune regulation. His work has been instrumental in linking genetic mutations to dis-regulated immune responses, providing the foundation for modern immunotherapies.
Shimon Sakaguchi
Shimon Sakaguchi holds an M.D. and Ph.D. from Kyoto University and is a Distinguished Professor at Osaka University’s Immunology Frontier Research Center. Sakaguchi’s pioneering studies in 1995 revealed the existence of regulatory T cells, showing that immune self-tolerance is actively maintained in peripheral tissues. His work laid the conceptual groundwork that allowed Brunkow and Ramsdell to connect genetic mechanisms to immune regulation.
The takeaway
The discoveries by Brunkow, Ramsdell, and Sakaguchi have fundamentally reshaped immunology, providing a deeper understanding of how the immune system protects the body from self-attack. By linking regulatory T cells to genetic mechanisms and human disease, they have launched a new era of research and therapies that harness the body’s own regulatory systems. Their work exemplifies the Nobel Prize’s mission of honoring scientific breakthroughs that deliver the greatest benefit to humankind.
