Nobel Peace Prize 2025: It was 1am at night, when Mary Brunkow's phone began to ring, assuming it to be a spam call, she put it on "do not disturb" and went back to sleep. Her husband too ignored the rings, only to be woken up along with their dog a few minutes later, when the Associated Press photographer showed up at their door. This is when Brunkow realized that she had won a Nobel Prize. Brunkow along with two other scientists Fred Ramsdell and Shimon Sakaguchi had won the Nobel Prize "for their discoveries concerning peripheral immune tolerance". What Is " peripheral immune tolerance"?It refers to the mechanisms by which the immune system prevents self-reactive immune cells, especially the T-cells from attacking healthy tissues once they are already in the body's circulation. The three are award for their work that revealed the existence and function of these special class of T-cell, called the regulatory T-cells, which act as brakes on immune responses, preventing autoreactivity. They also discovered the gene FOXP3, whose proper function is essential to the development and operation of regulatory T-cells. Their discovery revealed that mutation in FOXP3 genes is what leads to serious autoimmune disorders. How Did The Discovery Happen?Long before FOXP3, Sakaguchi, who is a professor at Osaka University in Japan, resurrected and rigorously defined the concept of regulatory T cells, also called Tregs. In 1995, he published work that showed that a subset of T-cells marked by CD25 along with CD4 could suppress autoimmune responses in mice. Those cells would be later called as the regulatory T-cell. It was his discovery which became the "brake" the immune system needed. Why Does This Discovery Matter?Before Sakaguchi's work, the existence of regulatory T-cells was speculative, even controversial. The idea was dismissed because the evidence was murky. His work also opened the possibility that one day we may enhance regulatory T-cell functions in autoimmune diseases or inhibit it in cancer settings. What Did Brunkow and Ramsdell Do?While Sakaguchi defined the Treg population, Brunkow and Ramsdell filled the gap by discovering FOXP3, the gene whose expression is necessary for Treg development. They studied that in mice, a peculiar strain known as "scurfy" mice, spontaneously developed lethal autoimmunity, which was manifested by scaly, flaky skin, enlarged lymph nodes and spleens, and early death. They showed that the scurfy phenotype is caused by a mutation on the X chromosome in a previously unknown gene which they named FOXP3. Their discovery also showed that in humans, a rare autoimmune syndrome called IPEX, which is characterized by immune dysregulation, polyedendocrinopathy, entropathy, X-linked inheritance is caused by mutations in the human equivalent, FOXP3. They thus, directly connected the mouse mutation and human disease that proved that FOXP3 is central to immune self-tolerance. Without functional FOXP3, regulatory T-cells fail to form or function, and immune system launches damaging attacks on normal tissues. What Comes Next?Their discovery is important as it can be used to treat autoimmune diseases like Type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and many more. The scope for cancer immunotherapy and tolerance during organ transplantation also broadens with the discovery. As with the FOXP3, it becomes possible to design therapies that block Treg suppression locally, enabling the immune system to better recognize and attack tumors. In terms of organ transplantation, with Tregs, it may become feasible to engineer Tregs that home to transplanted organs and locally suppress rejection.The Nobel press release and news sources note that more than 200 clinical trials are already underway based on regulatory T cell / peripheral tolerance ideas.
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