It’s the body’s first line of defense, shielding us from harmful microbes, viruses, and other invaders that attack and cause illness. But sometimes the human immune system fails or turns on itself to attack healthy cells and promote autoimmune diseases, like cancer, rheumatoid arthritis, and type 1 diabetes. For three scientists who conducted fundamental research on peripheral immune tolerance, a system that slows down the immune system and keeps it from harming the body, the result was a wealth of knowledge — and the 2025 Nobel Prize in Physiology or Medicine.
Recognition Brings Hope for Future Progress
“Only three people can be recognized for the Nobel Prize, but there are so many pioneers who worked on this,” said Maria-Luisa Alegre, a professor of medicine at the University of Chicago whose lab specializes in T cell responses during organ transplantation. Alegre noted that the Nobel recognition “gives us a lot of further momentum in trying to develop therapies for transplantation as well as for autoimmunity. I’m just thrilled, really, that this is the field that has been chosen.”
The three prizewinners, Mary E. Brunkow, a senior program manager at the Institute for Systems Biology in Seattle; Fred Ramsdell, a scientific advisor for Sonoma Biotherapeutics in San Francisco; and Shimon Sakaguchi a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan, were recognized by the Nobel Committee for a body of work that promises to spur clinical trials on potential new treatments, including therapies that may propagate regulatory T cells that can suppress overreactive immune responses in an autoimmune disease or organ transplant.
“This year’s Nobel Prize in Physiology or Medicine relates to how we keep our immune system under control so we can fight all imaginable microbes and still avoid autoimmune disease,” said Marie Wahren-Herlenius, a member of the 2025 Nobel Committee for Physiology or Medicine.
The Search for T Cells
It’s a theme that resonates throughout the world of medicine. Chronic inflammation and immune dysfunction are central drivers in over 60% of all deaths worldwide and underpin many chronic diseases, including cardiovascular disease, diabetes, cancer, and autoimmune disorders. This means that clinicians need to understand the ways that immunity impacts chronic disease and develop the tools and knowledge to comprehensively assess and treat immune-related chronic illness.
Back in the 1970s, scientists first proposed the idea that a distinct population of T cells (called suppressor T cells at the time) could suppress the immune response and potentially unlock a new understanding of the immune system and autoimmune disease. The theory was abandoned when early experiments failed to prove the existence of these cells.
Years later, Sakaguchi, then an immunologist at Aichi Cancer Center Research Institute in Nagoya, Japan, picked up the work on suppressor T cells.
“The basic hope was to discover a telltale molecular feature at the surface of such cells—a ‘marker’ by which suppressor T cells could be distinguished from other cells,” he wrote in a 2006 article for Scientific American that was coauthored by immunologist Zoltan Fehervari.
By focusing on the thymus, an organ located in the chest where T cells mature and are taught to avoid targeting healthy cells, Sakaguchi and his colleagues discovered cells that had an additional novel surface protein, CD25, which appeared necessary to prevent the immune system from attacking the body itself. This discovery of CD25, first detailed in a key 1995 paper in the Journal of Immunology, helped Sakaguchi establish the new class of T cells, which he called regulatory T cells.
Changing the Field
Soon, Brunkow and Ramsdell, then researchers at Celltech Chiroscience — a Washington State biotech company that focused on developing autoimmune disease therapies — looked into the genetic underpinnings of regulatory T cells and their role in immune system activity. By analyzing genes in healthy and scurfy mice, the team pinpointed a mutant gene called FOXP3 as the key gene responsible for autoimmunity in the diseased mice. They later found that mutations in this gene also caused a severe autoimmune disease, IPEX (short for immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome), in humans. These findings allowed Sakaguchi and researchers at other labs to confirm that FOXP3 controlled T regulatory cell development.
“The identification of this gene, FOXP3, was the discovery that changed the field, because now there was a molecular basis for immune regulation by T regulatory cells and immune tolerance,” said immunologist Jeffrey Bluestone, who co-founded Sonoma Biotherapeutics alongside Nobel winner Ramsdell. “That was the defining moment in the early 2000s when all of a sudden, this became real.”
These were the fundamental discoveries that moved the field forward, encouraging research groups and companies to tap these cells for new treatments and resulting in more than 200 clinical trials on therapies investigating such peripheral immune tolerance that are now in the works.
Understanding the Immune Code
These clinical trials are the key to unlocking the immune code and providing relief for a staggering number of patients. Chronic inflammation, a hallmark of immune imbalance, affects approximately 1 in 3 adults worldwide and plays a central role in the development and progression of chronic diseases such as arthritis, cardiovascular disease, Alzheimer’s, diabetes, and metabolic syndrome (Calder et al., 2021). The research being carried out right now has the potential to ultimately improve patient outcomes and quality of life.
In fact, autoimmune diseases impact nearly 50 million Americans, disproportionately affecting women, with many cases remaining undiagnosed for years, underscoring the need for early immune system assessment and intervention (National Institutes of Health, 2023). And emerging science reveals that dysregulated immune responses contribute not only to chronic disease but also to accelerated biological aging and reduced overall health span (Franceschi et al., 2018).
For clinicians aiming to enhance prevention, early detection, and personalized management of chronic illness, optimizing immune health is critical.
This October, experts in immune function will gather in Boston, MA, for a focused two-day course designed to break down the complex science of immune dysregulation and provide practical, evidence-based clinical strategies. Immune Code: Unlocking the Link Between Immunity & Chronic Disease is rooted in systems biology and personalized medicine, empowering you to restore immune balance, reduce chronic inflammation, and improve patient outcomes.
Join us at Immune Code: Unlocking the Link Between Immunity & Chronic Disease between October 24-25, 2025, for a weekend of immersion in the very latest research on immune function. You’ll find a depth of educational resources designed to transform care pathways for some of the most pervasive and complex health challenges today, and take away clinical applications relevant to your practice. Learn more and sign up by clicking here.