The Nobel Assembly at the Karolinska Institute in Sweden has awarded the 2025 Nobel Prize in Physiology or Medicine to American scientists Mary E. Brunkow and Fred Ramsdell, alongside Japanese researcher Shimon Sakaguchi. Their work has significantly advanced the understanding of how the immune system maintains self-regulation, preventing it from attacking the body's own healthy tissues. This fundamental insight has not only solved a long-standing biological puzzle but has also opened doors for new therapeutic strategies.
The laureates identified a critical safety network within the immune system, orchestrated by regulatory T cells (Tregs). These cells act as the immune system's internal regulators, applying the brakes to prevent overactive responses. Their groundbreaking research elucidated the concept of "peripheral immune tolerance," a crucial process that ensures the immune system distinguishes between foreign invaders and the body's own components. This discovery is significant because it revealed a secondary, peripheral mechanism essential for preventing self-reactive immune cells from causing harm, complementing the previously understood central tolerance established in the thymus.
Shimon Sakaguchi's pivotal research in the mid-1990s identified regulatory T cells as a distinct subset of T cells that actively control other immune cells. His work demonstrated that the absence of these cells in mice led to autoimmune disease, while their restoration mitigated such attacks. In 2001, Mary E. Brunkow and Fred Ramsdell furthered this understanding by identifying the genetic basis for a severe autoimmune syndrome in mice, pinpointing mutations in the FOXP3 gene. This discovery also linked to human autoimmune conditions like IPEX syndrome, and subsequent research by Shimon Sakaguchi confirmed FOXP3 as the master regulator for the development of regulatory T cells.
The implications of these discoveries are far-reaching, offering new hope for treating a range of debilitating conditions. The identification of regulatory T cells has opened avenues for innovative therapeutic strategies in autoimmune diseases, such as multiple sclerosis. Furthermore, this research is instrumental in enhancing cancer immunotherapies and is being explored to improve outcomes in organ transplantation by modulating immune responses to prevent rejection. The prize, carrying a cash award of 11 million Swedish kronor (approximately $1 million), recognizes the profound impact of this fundamental biological insight on human health. Ongoing clinical trials based on this research underscore the transformative potential of understanding and manipulating the immune system's self-regulatory capabilities.