2025 Nobel Prize for Physiology or Medicine for Discoveries on Regulation of the Immune System

“I think it is fair to say that the Nobel Prize is the highest honor any scientist or artist can achieve.”

Lester Bowles Pearson, Canadian diplomat, 1957 Nobel Peace Prize laureate

“The 2025 Nobel Prize in Physiology or Medicine was awarded to the scientists who conducted fundamental research on peripheral immune tolerance, a system that pumps the brakes on the immune system and keeps it from harming the body.”

Lauren J. Young, science journalist, associate editor, Scientific American

The Nobel Prize is arguably the most prestigious honor in science, literature, and diplomacy. This year’s Nobel Prize for Physiology or Medicine was awarded to two American scientists, Mary Brunkow, at the Hood Lab, Institute for Systems Biology in Seattle, and Fred Ramsdell, an immunologist at Sonoma Biotherapeutics in Elmhurst, Illinois, and Japanese scientist, Shimon Sakaguchi, an immunologist at Osaka University. The trio received the award for their discoveries of how the immune system protects us from countless microbes and also, via “regulatory T cells,” prevents immune cells from attacking our body tissues, thereby averting autoimmune diseases. In this week’s Germ Gems post, I provide a brief history of the Nobel Prizes and put the scientific discoveries of this year’s physiology or medicine awardees into an infectious diseases perspective.

The Nobel Prize, a dynamite idea. Alfred Nobel (1833-1896), a Swedish chemist and inventor, made a fortune from the invention of dynamite and other explosives. When he died, he donated his fortune to a foundation to fund the Nobel Prizes. Nobel specified that the prizes were to be awarded in the following areas: Physiology or Medicine, Physics, Chemistry, Literature and Peace. (The Nobel Prize for Economics was established in 1968 by an endowment from Sweden’s central bank.) He intended that the prizes be awarded annually for scientific discoveries that would be of the greatest benefit to humankind. Each prize consists of a medal, diploma, and cash award. It is, however, the profound honor of recognition by an elite group of peers that makes this a unique and highly coveted award.

In 1901, Emil von Behring received the first Nobel Prize in Physiology or Medicine for his work on serum therapy and its application against diphtheria. Since then, the Nobel Assembly, a group of 50 professors at the Karolinska Institutet in Stockholm, Sweden, has awarded 116 prizes for groundbreaking discoveries in physiology or medicine. Up through 2025, at least 14 Nobel Prizes were awarded, like this year’s award, for work directly connected to immunology.

The “immune response:” a double-edged sword (a recap). Human health is dependent upon the immune system. It is the complex and finely tuned response of cells of the immune system—T, B, and NK lymphocytes, as well as phagocytic cells: neutrophils and monocytes/macrophages— that protect us from invading microbes, as well as from enemies within, i.e., cancer cells. The immune system is, however, a double-edged sword as there is a price to be paid for its protection. Mediators released from activated immune cells, such as cytokines and reactive oxygen and nitrogen species, make us feel sick, cause tissue damage, and can, in some cases of severe sepsis, even kill us.

Understanding the “double-edged sword” nature of the immune system can be traced to Rudolph Virchow, a 19^th century German physician and pathologist who developed the concept of cellular pathology. Virchow provided insight into the basis for the four cardinal signs of inflammation, originally described in the 1^st century CE by the Roman physician Cornelius Celsus: rubor (redness). swelling (tumor), heat (calor), and pain (dolor), to which Virchow added a fifth sign, function lessa (loss of function).

Contributions of the 2025 Nobel laureates. Autoimmune diseases are disorders in which immune cells mistakenly turn on cells of the body and include, but are not limited to,  rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. This year’s Nobel awardees discovered a class of cells that help prevent the body from attacking its own tissues.

Their key discoveries relate to a subset of T lymphocytes called T regulatory cells (Tregs).

These cells play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. They do this by releasing inhibitory cytokines (interleukin [IL] 10 and 35, and TGF-beta), directly suppressing autoreactive T cells and antigen-presenting cells, modulating dendritic cell function, and consuming IL-2 to limit effector T cell proliferation.

In the early 2000s, Ramsdell and Brunkow studied scurfy mice and were able to pinpoint a “mutant gene called FOXP3 as the gene responsible for autoimmunity in the diseased mice.” (Young, L., “2025 Nobel Prize in Physiology or Medicine Awarded for Discoveries of How the Body Puts the Brakes on the Immune System,” Scientific American, October 6, 2025). Their findings enabled Sakaguchi and researchers at other labs to confirm that FOXP3 controlled T regulatory cell development. The discovery of the gene, FoxP3, changed the field, because now there was a molecular basis for understanding immune regulation by Tregs and immune tolerance.  

The work of Brunkow, Ramsdell and Sakaguchi “answered a fundamental question in biomedicine and paved the way for new treatment strategies in cancer, autoimmunity and transplantation medicine.” (van den Heuvel, M., “2025 Nobel Prize Honors Discovery of Immune System ‘Brake,’” Medscape, October 8, 2025). Their discoveries spurred a number of research groups and companies to investigate basic functions of Tregs in autoimmune diseases, cancers, and transplantation. According to the Nobel Committee members, more than 200 clinical trials are in the works on therapies investigating peripheral immune tolerance.

In a summary of the accomplishments of Brunkow, Ramsdell, and Sakaguchi, the Nobel Committee stated: “Through their revolutionary discoveries, [they] have provided fundamental knowledge of how the immune system is regulated and kept in check. Thus they have conferred the greatest benefit to humankind.”

What’s next? By most metrics, 2025 has been the worst year in modern history for the American scientific enterprise because of the deep cuts to the nation’s science funding by the current administration including more than $1 billion to the National Science Foundation and $4.5 billion to the National Institutes of Health. (Burdick, A., “Highs and lows in science,” New York Times, October 10, 2025). And next year looks to be worse.

The Trump administration proposes to cut the National Oceanic and Atmospheric Administration (NOAA) funding by $1.8 billion in 2026. Although it’s easy to say that scientists and post-doctoral students just need to “weather the storm,” with the cuts to the NOAA we will not even know what the storm is or where it will hit. We do know, however. that medical science and research will suffer greatly from the cuts.

It takes years to make scientific discoveries that are ultimately proven to be beneficial to human health and humankind. But scientific discoveries take dedication and funding. The dedication of scientists like this year’s Nobel Prize laureates in Physiology or Medicine is extraordinary. The burning question, I believe, is when will the pendulum swing back to sensible governmental support (funding), especially of young investigators who can keep the pipeline of new ideas and treatments flowing? For all of our sakes,  let’s hope it is soon.