Nobel Prize: Discoveries That Prevent Autoimmunity
The 2025 Nobel Prize in Physiology or Medicine has been awarded to
Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi
for their discovery of a class of immune cells that help to prevent the body from attacking its own tissues.
Their landmark discoveries of regulatory T cells (Tregs) and the FOXP3 gene transformed understanding of immune tolerance and opened the door to new treatments for autoimmune disease.
In 1995, Sakaguchi identified regulatory T cells, a rare subset of T cells that act as the immune system’s “brakes,” shutting down excessive inflammation and maintaining balance. Without them, autoimmune diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis can develop. Brunkow and Ramsdell later discovered that mutations in the FOXP3 gene lead to fatal autoimmune diseases in mice and humans, demonstrating that FOXP3 is crucial for Treg development and function.
These discoveries have since spurred hundreds of studies and more than 200 ongoing clinical trials exploring how to harness Tregs to treat autoimmune and inflammatory disorders.
Companies including Eli Lilly, Celgene, and Sonoma Biotherapeutics are now developing therapies that stimulate or expand Tregs to restore immune tolerance in diseases such as lupus, autoimmune hepatitis, and rheumatoid arthritis.
Experts describe the Nobel-winning work as a foundation for a new generation of “immune-calming” treatments that could one day prevent or even cure autoimmunity. During a press conference, Sakaguchi shared an encouraging message for young researchers:
“Keep going, find your path, and continue doing what you love.”
Citations
Conrad, N., Misra, S., Verbakel, J. Y., Verbeke, G., Molenberghs, G., Taylor, P. N., Mason, J., Sattar, N., McMurray, J. J. V., McInnes, I. B., Khunti, K., & Cambridge, G. (2023). Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet (London, England), 401(10391), 1878–1890. https://doi.org/10.1016/S0140-6736(23)00457-9
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of immunology (Baltimore, Md. : 1950), 155(3), 1151–1164.
Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B., Clark, L. B., Yasayko, S. A., Wilkinson, J. E., Galas, D., Ziegler, S. F., & Ramsdell, F. (2001). Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nature genetics, 27(1), 68–73. https://doi.org/10.1038/83784
Wildin, R. S., Ramsdell, F., Peake, J., Faravelli, F., Casanova, J. L., Buist, N., Levy-Lahad, E., Mazzella, M., Goulet, O., Perroni, L., Bricarelli, F. D., Byrne, G., McEuen, M., Proll, S., Appleby, M., & Brunkow, M. E. (2001). X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nature genetics, 27(1), 18–20. https://doi.org/10.1038/83707
Hori, S., Nomura, T., & Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science (New York, N.Y.), 299(5609), 1057–1061. https://doi.org/10.1126/science.1079490