Core Points - The 2025 Nobel Prize in Physiology or Medicine was awarded to scientists Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries in peripheral immune tolerance mechanisms [1][3] - The prize amount is 11 million Swedish Krona, approximately 8.34 million RMB, to be shared among the winners [3] Group 1: Research Contributions - The winners identified regulatory T cells as "guardians" of the immune system, which prevent immune cells from attacking the body's own tissues [4][8] - They discovered the "master switch" gene Foxp3, which controls the development and function of these key cells, explaining why the immune system does not attack itself [4][8] - Their findings have laid the groundwork for new research areas and have facilitated the development of therapies for diseases such as type 1 diabetes and rheumatoid arthritis [8] Group 2: Background of Winners - Mary E. Brunkow, born in 1961, obtained her PhD in molecular biology from Princeton University in 1991, focusing on the intersection of biomedicine, immunology, and systems biology [3] - Fred Ramsdell, born in 1960, has been active in both basic research and the biotechnology industry, working on translating immunological discoveries into therapeutic strategies [3] - Shimon Sakaguchi, born in 1951, is a professor at Osaka University and has received multiple awards for his pioneering work in immune regulation [3] Group 3: Historical Context - Sakaguchi's initial discovery in 1995 contradicted the prevailing belief that immune tolerance was solely achieved through central tolerance in the thymus [5][6] - Brunkow and Ramsdell focused on a mutant mouse model, "scurfy," which exhibited uncontrolled T cell proliferation due to a genetic defect, leading to their identification of the Foxp3 gene in 2001 [7] - The integration of these discoveries by Sakaguchi in 2003 provided a comprehensive understanding of immune regulation mechanisms [8]

Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries in peripheral immune tolerance, which have opened new research avenues and advanced therapies for cancer and autoimmune diseases [1][6]. Group 1: Immune System Functionality - The immune system protects humans from thousands of viruses and bacteria daily, and its ability to distinguish between pathogens and self-cells is crucial for survival [1]. - T cells possess a unique protein called T cell receptors that act as sensors to identify whether the body is under attack, with the potential to create over 10^15 different T cell receptors [1][2]. Group 2: Research Breakthroughs - In the 1980s, researchers identified a selection process called "central tolerance" that eliminates T cells that mistakenly attack the body's own tissues during their maturation in the thymus [2]. - Shimon Sakaguchi proposed the existence of "regulatory T cells" as a mechanism to calm other T cells, leading to the discovery of this new T cell type after over a decade of research [2][5]. Group 3: Genetic Discoveries - In the 1940s, researchers discovered "scurfy" mice that suffered from severe immune system issues due to T cell attacks on their organs, leading to the investigation of the underlying genetic causes [3][4]. - Mary E. Brunkow and Fred Ramsdell identified the Foxp3 gene, which is linked to the IPEX autoimmune disease and is crucial for the development of regulatory T cells [4][5]. Group 4: Therapeutic Implications - The findings regarding regulatory T cells have spurred the development of potential new therapies, including the isolation and amplification of these cells from patients to enhance their immune response [6]. - Researchers are exploring methods to modify regulatory T cells to target specific organs, thereby protecting them from immune system attacks [6].

Core Points - The Nobel Prize in Physiology or Medicine was awarded to Shimon Sakaguchi and two American scientists for their discoveries in peripheral immune tolerance [1][2] - This recognition highlights the importance of immune system regulation in preventing autoimmune diseases while combating pathogens [2][3] Group 1: Research Findings - The research revealed key mechanisms by which the immune system avoids attacking its own tissues, paving the way for new treatments for autoimmune diseases, cancer, and organ transplantation [2][4] - Sakaguchi discovered a previously unrecognized subset of T cells, challenging the traditional view that immune tolerance is achieved solely through the elimination of abnormal T cells in the thymus [2][3] Group 2: Clinical Applications - Despite the groundbreaking discoveries, the transition to clinical applications remains a significant challenge due to the complexity of human diseases and the heterogeneity of regulatory T cells [4][5] - Current research is focused on inducing immune tolerance and addressing rejection in organ transplantation, with several therapies based on regulatory T cells in clinical trials [5] Group 3: Future Prospects - There is optimism that as understanding of disease mechanisms deepens, immune therapies will evolve towards more precise regulatory approaches [5] - However, challenges such as ensuring the stability and specificity of regulatory T cells in clinical settings persist, which may limit their application compared to other therapies like CAR-T cell treatments [5]

Group 1 - The Nobel Prize in Physiology or Medicine was awarded to Japanese scientist Shimon Sakaguchi and two American scientists, Mary Brunkow and Fred Ramsdell, for their discoveries in peripheral immune tolerance [1][2] - Shimon Sakaguchi is the third Japanese scientist to receive this award in the last decade, following Yoshinori Ohsumi in 2016 and Tasuku Honjo in 2018, with both previous awards also related to immune regulation [1] - The research of the awardees reveals key mechanisms by which the immune system avoids attacking its own tissues, opening new directions for treatments of autoimmune diseases, cancer, and organ transplantation [2][3] Group 2 - The findings of the awardees establish a foundation for new research areas and promote the development of new therapies targeting cancer and autoimmune diseases [2] - Sakaguchi's research identified a previously unrecognized subset of T cells, challenging the traditional understanding that immune tolerance is achieved solely through the elimination of abnormal T cells in the thymus [3] - The role of regulatory T cells as "peacekeepers" in the immune system is emphasized, as they suppress abnormal immune responses to maintain self-tolerance and prevent autoimmune diseases [3][4] Group 3 - Despite the significant findings, the clinical application of these discoveries is still a long way off, with challenges in translating the research into effective therapies for autoimmune diseases and organ transplantation [4][5] - The complexity of human diseases, involving interactions between genes and the environment, complicates the clinical application of therapies based on regulatory T cells [5] - Current research is underway to induce immune tolerance and address rejection reactions in organ transplantation, but the path to successful clinical application remains challenging [4][5]