Nowadays finding a mutation on the X chromosome would be relatively easy. But in the 1990s it was a labor -intensive effort. After reducing the location of the mutation to a piece of 500,000 nucleotides that include 20 genes, she carefully scanned 19 of them before they found a mutation in the very last one; It was a small insertion with two bases that threw the coding from the frame and resulted in a lagging protein. The mutated gene had never been studied before, but it looked like others who were classified as fork head/winged helix genes, so Brunkow and Ramsdell called it it Foxp3.
The couple then did genetic rescue experiments, where it became normal Foxp3 Genes back in scurfy mice – for a good measure in five lines. The genetic rescue prevented the serious car -immune disease in the male scurfy mice and confirmed that the mutant Foxp3 was the source of the problem. The researchers then connected dots between scurfy mice and a disease in people, called Ipex (immune regulation, polyendocrinopathy, enteropathy, X-bound). Ipex causes a fatal car -immune disease in young boys. Brunkow and Ramsdell showed that mutations in the human version of Foxp3 were also behind Ipex, which they published in 2001, together with all their scurfy findings.
Compile
Back in Japan, the Sakaguchi team connected more dots in the two years thereafter, that realizing that that Foxp3 Was selectively enabled in their regulator T cells. Furthermore, if they forced ordinary t -helper cells to activate Foxp3, Those cells then became regulating T cells.
It appears that the FOXP3 protein is the master control for regulating T cells. That is, it is a protein that controls the activity of a large series of genes that jointly give T cells the ability to stop car -immune response and to dampen strong immune response after an infection has been erased.
In general, the findings have opened new lines of research into peripheral immunolerance. Researchers are now working well to manipulate regulatory T cells, such as ensuring that they cannot protect cancer -like tumors, engineer to treat car -immune diseases and to recruit them to specifically protect transplanted organs and tissues.
The collective work to discover and understand the regulatory cells caused fundamental knowledge about how our immune system works, the Nobel Committee concluded: “They have therefore granted the greatest benefit to humanity.”
