Nobel Prize Awarded for Breakthroughs in Immune Tolerance

On October 6, 2025, the Nobel Assembly at the 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 fundamentally transformed the understanding of the immune system's self-regulation, particularly through the identification and elucidation of regulatory T cells (Tregs). These cells play a crucial role in preventing autoimmune diseases by ensuring the immune system does not attack the body's own tissues.

Peripheral immune tolerance is a critical mechanism that prevents the immune system from attacking the body's own tissues, thereby averting autoimmune diseases. Central to this process are regulatory T cells (Tregs), a subset of T cells that suppress overactive immune responses. The discovery and understanding of Tregs have significantly advanced immunology, leading to potential therapeutic applications for autoimmune diseases, cancer, and organ transplantation.

In 1995, Shimon Sakaguchi identified regulatory T cells, challenging the prevailing belief that immune tolerance was solely established in the thymus through central tolerance. His work demonstrated that the immune system possesses additional layers of regulation to prevent self-attack.

In 2001, while working together at Celltech Chiroscience in Bothell, Washington, Mary E. Brunkow and Fred Ramsdell discovered the Foxp3 gene. They found that mutations in this gene lead to severe autoimmune conditions, such as IPEX syndrome, highlighting its crucial role in the development and function of regulatory T cells.

In 2003, Sakaguchi linked these findings by demonstrating that the Foxp3 gene governs the development of regulatory T cells, solidifying the connection between genetic factors and immune regulation.

Mary E. Brunkow, born in 1961, earned her Ph.D. in molecular biology from Princeton University. She currently serves as a Senior Program Manager at the Institute for Systems Biology in Seattle, USA.

Fred Ramsdell, born in 1960, obtained his Ph.D. in microbiology and immunology from the University of California, Los Angeles. He is a Scientific Advisor at Sonoma Biotherapeutics in San Francisco, USA.

Shimon Sakaguchi, born in 1951, received 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 profound implications for public health. By elucidating the mechanisms of immune regulation, their work has paved the way for novel treatments for autoimmune diseases, such as rheumatoid arthritis and Type 1 diabetes, and has potential applications in cancer immunotherapy and improving outcomes in organ transplantation.

Fred Ramsdell was on a remote camping trip in Wyoming when the Nobel announcement was made. Due to being off the grid, he only learned of the award the following day when his wife turned on her phone while fixing their car. This delay in communication added a unique twist to the announcement.

This award marks the 116th Nobel Prize in Physiology or Medicine since its inception in 1901. Mary E. Brunkow becomes the 14th woman to receive this honor, highlighting the ongoing progress toward gender diversity in the sciences.

The Nobel Assembly's recognition of Brunkow, Ramsdell, and Sakaguchi underscores the critical importance of understanding immune regulation. Their collective work has not only deepened scientific knowledge but also opened new avenues for treating a range of diseases, offering hope to millions worldwide.