Discovery of cells that keep the immune reactions under control, the Nobel Prize in Medicine

Nowadays finding a mutation on the X chromosome would be relatively easy. But in the 1990s it was a labor -intensive effort. After they had reduced the location of the mutation to a piece of 500,000 nucleotides that include twenty genes, they carefully scanded 19 before they found a mutation in the very lastest; It was a small insertion of two base pairs that threw the coding from the frame and resulted in an imperfected protein. The mutated gene had never been investigated before, but it looked like other genes that were classified as forkhead/winged-helix genes, so Brunkow and Ramsdell called it Foxp3.

The couple then did genetic rescue experts, which became normal Foxp3 Genes back in scabby mice – for the record in five lines. The genetic rescue prevented the serious autoimmune disease in the male scurvy mice and confirmed that the mutant Foxp3 was the source of the problem. The researchers then brought points in connection between scabby mice and a disease in people, called Ipex (immune disregulation, polyendocrinopathy, enteropathy, x-linked). Ipex causes a deadly autoimmune disease in young boys. Brunkow and Ramsdell showed that mutations in the human version of Foxp3 were also behind Ipex, which they published together with all their filthy findings in 2001.

Assembling

Back in Japan, the Sakaguchi team connected more and more points in the two years after that they realized that Foxp3 was selectively encouraged in their regulatory T cells. Furthermore, if they forced regular T helper cells to activate Foxp3, Those cells then became regulating T cells.

It appears that the FOXP3 protein is the main check for regulating T cells. That is, it is a protein that checks the activity of a large series of genes that together give T cells the ability to stop autoimmune reactions and to temper strong immune reactions after an infection has disappeared.

Overall, the findings have opened new lines of research into peripheral immune tolerance. Researchers are now working on manipulating regulatory T cells forever, by ensuring that they cannot protect cancer tumors, develop them to treat autoimmune diseases and to recruit them to protect specifically transplanted organs and tissues.

The collective work to discover and understand T-regulating cells provided fundamental knowledge about how our immune system works, the Nobel Committee concluded: “They have therefore delivered the biggest advantage for humanity.”