\n<\/p>\n
This story has been updated.<\/p>\n
The human immune system is our body\u2019s primary line of defense against harmful microbes, viruses and other invaders\u2014but that defense line can sometimes run amok and attack healthy cells. This is the basis of many autoimmune diseases, from cancer to rheumatoid arthritis to type 1 diabetes. 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.<\/p>\n
Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi jointly won the prize, which was announced on Monday in Stockholm. Sakaguchi is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan. Brunkow is now a senior program manager at the Institute for Systems Biology in Seattle and Ramsdell is a scientific advisor for Sonoma Biotherapeutics in San Francisco. The Nobel Committee recognized the awardees\u2019 body of work for spurring clinical trials on potential new treatments, such as therapies that may propagate immune cells called regulatory T cells that can suppress overreactive immune responses in an autoimmune disease or organ transplant.<\/p>\n
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\u201cThis year\u2019s 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,\u201d said Marie Wahren-Herlenius, a member of the 2025 Nobel Committee for Physiology or Medicine, at a livestreamed press conference today in Stockholm.<\/p>\n
\u201cOnly three people can be recognized for the Nobel Prize, but there are so many pioneers who worked on this,\u201d says Maria-Luisa Alegre, a professor of medicine at the University of Chicago. Her lab specializes in T cell responses during organ transplantation. The Nobel recognition \u201cgives us a lot of further momentum in trying to develop therapies for transplantation as well as for autoimmunity. I\u2019m just thrilled, really, that this is the field that has been chosen.\u201d<\/p>\n
Around the 1970s scientists first proposed that there might be a distinct population of T cells that can suppress the immune response. It was thought that such T cells, dubbed suppressor T cells at the time, could potentially unlock a new understanding of the immune system\u2014and of autoimmune disease. Early experiments trying to prove the existence of these cells came up empty handed, however; the theory was ultimately abandoned as being too fringe.<\/p>\n
The early research \u201cidentified activities without clear molecular understanding,\u201d says immunologist Jeffrey Bluestone, who co-founded Sonoma Biotherapeutics alongside Nobel winner Ramsdell. \u201cSome of the work was hard to replicate, and so by the end of the decade, a lot of people were very skeptical that such a system existed.\u201d<\/p>\n
Years later, Sakaguchi, then an immunologist at Aichi Cancer Center Research Institute in Nagoya, Japan, picked up the work on suppressor T cells. \u201cThe basic hope was to discover a telltale molecular feature at the surface of such cells\u2014a \u2018marker\u2019 by which suppressor T cells could be distinguished from other cells,\u201d Sakaguchi wrote in a 2006 article for Scientific American that was coauthored by immunologist Zoltan Fehervari, now a senior editor at Nature.<\/p>\n
Sakaguchi and his colleagues focused on the thymus, an organ located in the chest where T cells mature and are taught to avoid targeting healthy cells. The thymus is supposed to eliminate any faulty T cells\u2014but in certain autoimmune conditions, these bad actors can fly under the radar. In a series of experiments on mice, Sakaguchi found that helper T cells produced in the thymus (identified by the surface protein CD4) didn\u2019t all function the same way. Cells that had an additional novel surface protein, CD25, appeared necessary to prevent the immune system from attacking the body itself. In experiments in which Sakaguchi and his colleagues wiped the mice of T cells with CD25, various organs\u2014thyroid, stomach, gonads, pancreas and salivary glands\u2014succumbed to white blood cell attacks and resulted in \u201cdramatic inflammation,\u201d Sakaguchi and Fehervari wrote in Scientific American.<\/p>\n
The 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 dubbed regulatory T cells.<\/p>\n
\u201cIt wasn\u2019t a high-profile paper at the time. He was just sort of plugging away, publishing paper after paper on this topic to refine his findings,\u201d says Peter Savage, a professor of pathology at the University of Chicago who studies regulatory T cells. \u201cThe idea of suppressor cells had fallen out of favor. It was Sakaguchi who really, through a meticulous series of experiments, pursued this idea and was able to define a population of CD4 T cells that had really potent suppressor activity or \u2018peacekeeper\u2019 activity.\u201d<\/p>\n
In Washington State, Brunkow and Ramsdell further cemented the role of regulatory T cells in immune system activity through several papers in 2001 that looked into the cells\u2019 genetic underpinnings. The two scientists were both then researchers at Celltech Chiroscience, a biotech company that focused on developing autoimmune disease therapies.<\/p>\n
To find out whether these peacekeeper cells were a unique lineage of T cells or just a transient population, Ramsdell and Brunkow studied scurfy mice\u2014a strain of mice unexpectedly born with scaly, crusty skin and swollen lymph nodes that lived for just a few weeks. 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. The researchers 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 genetic findings laid the groundwork for Sakaguchi and researchers at other labs, including Alexander Rudensky, who currently heads the immunology program at Memorial Sloan Kettering Cancer Center, to confirm that FOXP3 controlled T regulatory cell development.<\/p>\n
\u201cThe 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,\u201d Bluestone says. \u201cThat was the defining moment in the early 2000s when all of a sudden, this became real.”<\/p>\n
With these fundamental discoveries \u201cthe field was off and running,\u201d Savage says. The findings spurred research groups and companies to tap these cells for new treatments. More than 200 clinical trials on therapies investigating such peripheral immune tolerance are in the works, according to the Nobel Committee members. Savage\u2019s lab is studying the basic function and development of regulatory T cells and has a particular interest in cancer.<\/p>\n
Regulatory T cells are very commonly found in cancerous tumors, he says. \u201cThey\u2019re thought to dampen the anti-tumor immune response, and so there\u2019s a lot of interest in disabling or depleting these cells in the context of cancer therapy.\u201d<\/p>\n
Alternatively, other therapies are being developed to try to put lab-grown or genetically modified versions of these cells to work. For example, regulatory T cells are important in boosting organ transplant tolerance\u2014the body\u2019s ability to accept foreign tissue from a donor without triggering a vicious immune response. Alegre\u2019s team has shown in animal models that eliminating regulatory T cells at the time of transplantation causes the body to lose tolerance and reject the organ. \u201cThere are many labs that are trying to reinforce this transplantation tolerance or induce it more effectively by either expanding these regulatory T cells … or engineering regulatory T cells,\u201d she says.<\/p>\n
For expansion, the cells can be taken from a transplant recipient and copied in bulk. As they grow, you can make them multiply in response to antigens from the donor tissue, Alegre explains. The regulatory T cells can be reinfused at the time of the transplant or when the recipient is showing signs of organ rejection. Another approach takes regulatory T cells and engineers a chimeric antigen receptor (CAR). These regulatory CAR-T cells can express antibodies that specifically recognize and bind to cells on the transplanted organ, suppressing the immune response to it.<\/p>\n
\u201cThere\u2019s also research on genetic engineering to correct defects [in FOXP3],\u201d she says. \u201cThere are people who have a lot of inflammation in autoimmunity because their regulatory T cells are defective because of mutations in this master regulator.\u201d<\/p>\n
Bluestone says that researchers have also been working for the past couple decades on a regulatory T cell therapy that could effectively \u201cshut down unwanted autoimmune responses\u201d for diseases such as rheumatoid arthritis or type 1 diabetes.<\/p>\n
Sonoma Biotherapeutics is \u201cin the clinic now, as are a couple of other companies, trying to prove the efficacy of this new class of drugs,\u201d he says. \u201cI think there is a lot of excitement now about being able to harness the cells themselves as immunotherapies or drugs that will enhance the function of these cells.\u201d<\/p>\n
The team at Sonoma Biotherapeutics is planning on presenting data from its clinical trial of regulatory CAR-T cells in people with rheumatoid arthritis at the American College of Rheumatology meeting this month, Bluestone says.<\/p>\n
\u201cI used to think that some sort of reward may be forthcoming,\u201d Sakaguchi said in a press conference Monday, according to Reuters, \u201cif what we have been doing will advance a little further and it will become more beneficial to people in clinical settings.<\/p>\n","protected":false},"excerpt":{"rendered":"
This story has been updated. The human immune system is our body\u2019s primary line of defense against harmful microbes, viruses and other invaders\u2014but that defense line can sometimes run amok and attack healthy cells. This is the basis of many autoimmune diseases, from cancer to rheumatoid arthritis to type 1 diabetes. The 2025 Nobel Prize<\/p>\n","protected":false},"author":1,"featured_media":26321,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[50],"tags":[3256,3823,15451,4391,788,8015,13708,15822,1169,10484],"class_list":{"0":"post-26320","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-environment","8":"tag-autoimmune","9":"tag-awarded","10":"tag-discoveries","11":"tag-disease","12":"tag-key","13":"tag-medicine","14":"tag-nobel","15":"tag-physiology","16":"tag-prize","17":"tag-treating"},"_links":{"self":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/26320","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=26320"}],"version-history":[{"count":0,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/26320\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/media\/26321"}],"wp:attachment":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=26320"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=26320"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=26320"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}