Nobel Prize Awarded for Pioneering Discoveries in Immune Tolerance

On October 6, 2025, the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries concerning peripheral immune tolerance. Their research has significantly advanced the understanding of how the immune system distinguishes between self and non-self, preventing autoimmune diseases.

The immune system is a complex network designed to protect the body from harmful pathogens. A critical aspect of its function is the ability to recognize and tolerate the body's own tissues, a process known as immune tolerance. Disruptions in this process can lead to autoimmune diseases, where the immune system mistakenly attacks healthy cells.

In 1995, Shimon Sakaguchi identified a subset of T cells, now known as regulatory T cells (Tregs), which play a crucial role in suppressing immune responses against the body's own tissues. This discovery challenged the prevailing belief that immune tolerance was solely established in the thymus through central tolerance mechanisms. Sakaguchi's work demonstrated that peripheral mechanisms also contribute significantly to maintaining immune balance.

Building upon this foundation, Mary E. Brunkow and Fred Ramsdell, in 2001, discovered the Foxp3 gene. They found that mutations in this gene were linked to severe autoimmune conditions in mice, specifically the scurfy mouse model. Further research revealed that similar mutations in the human equivalent of this gene cause a serious autoimmune disease known as IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome). This work established a genetic basis for the development and function of regulatory T cells.

In 2003, Sakaguchi further elucidated the role of the Foxp3 gene by demonstrating that it governs the development of regulatory T cells. This finding connected the earlier discoveries and provided a comprehensive understanding of peripheral immune tolerance. Collectively, these contributions have reshaped the field of immunology and opened new avenues for therapeutic interventions.

Mary E. Brunkow, born in 1961, earned her Ph.D. from Princeton University. She is currently a Senior Program Manager at the Institute for Systems Biology in Seattle, USA. Fred Ramsdell, born in 1960, received his Ph.D. in 1987 from the University of California, Los Angeles. He serves as a Scientific Advisor at Sonoma Biotherapeutics in San Francisco, USA. Shimon Sakaguchi, born in 1951, obtained his M.D. in 1976 and Ph.D. in 1983 from Kyoto University, Japan. He is a Distinguished Professor at the Immunology Frontier Research Center, Osaka University, Japan.

The laureates' discoveries have had profound implications for medical science. Insights into regulatory T cells and the Foxp3 gene have paved the way for developing therapies targeting autoimmune diseases such as Type 1 diabetes, lupus, and rheumatoid arthritis. Manipulating regulatory T cells offers potential strategies to enhance anti-tumor immune responses, contributing to the development of novel cancer treatments. Additionally, understanding peripheral immune tolerance can improve transplant outcomes by reducing the risk of organ rejection.

The recognition of Brunkow, Ramsdell, and Sakaguchi underscores the importance of fundamental research in immunology and its translational potential. Their work has inspired over 200 clinical trials exploring regulatory T cell-based therapies, with companies like Sonoma Biotherapeutics and Quell Therapeutics at the forefront. This award also marks a significant milestone in the history of the Nobel Prize in Physiology or Medicine, highlighting the evolving understanding of the immune system. Notably, Brunkow becomes the 14th woman to receive this honor, reflecting progress toward gender diversity in scientific recognition.

The 2025 Nobel Prize in Physiology or Medicine honors transformative research that has reshaped the understanding of immune tolerance. The laureates' findings continue to influence therapeutic strategies, offering hope for patients with autoimmune diseases and cancer.