The 2025 Nobel Prize in Physiology or Medicine awarded to a trio of researchers for their work on peripheral immune tolerance, or how tissues and organs are saved from auto-immune attacks by rogue cells, is a recognition of its exciting potential to develop new therapies. Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi have been awarded the prize for explaining the mechanism by which specialist cells help weed out bad immune cells that attack healthy human tissues.
The discoveries by Prof. Sakaguchi of the role of specialist regulatory T cells containing a particular surface protein, CD25, in addition to another, CD4, and by Professors Brunkow and Ramsdell of the FOXP3 gene responsible for the proper development of specialist cells, have led to years of intensive work on finding new therapies for conditions such as type 1 diabetes and rheumatoid arthritis. Some of those efforts could also lead to the engineering of regulatory T cells in laboratories that would prevent immune attacks on tissues.
After a slow start in the 1970s, the progress made in the field, with a fair amount of work carried out in private laboratories also, has moved into prime time now, boosted greatly by the Nobel recognition. The research by Prof. Sakaguchi and colleagues on mice involving removal of the thymus gland—where regulatory cells are trained—rendered the mice unable to survive for long, since they could not develop the regulatory T cells that stop rogue cells from scoring self-goals against tissues and organs. Professors Brunkow and Ramsdell identified the role of a faulty FOXP3 gene in preventing the production of the specialist cells, thereby leading to a rare disease in boys called IPEX and a similar scaly-skin disease in scurfy mice.
It is a tribute to the strength of science, advanced by the prize-winning scientists and many more researchers in the field worldwide, that over 200 clinical trials are currently underway in the field to come up with therapeutic treatments for a host of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and type-1 diabetes. This is apart from the growing scourge, cancer, where the aggregation of regulatory T cells in the tumour must be broken to let the immune system do its job, and in organ transplants, where the introduced organ is attacked by the immune system, warranting the presence of more regulatory T cells to stop that.
In the latter example, a transplanted liver or kidney is afforded protection. Engineering beneficial regulatory T cells in a laboratory and injecting them to calm an overactive immune system is one approach. These potential therapies, grounded in prize-winning science, offer tremendous hope to millions who endure crippling diseases. The Nobel, with its scientific explanation of the immune system’s complexities, has an uplifting effect amidst obscurantist anti-science campaigns.
