Discovery of cells that keep immune responses in check wins medicine Nobel Prize

"After narrowing the mutation's location down to a stretch of 500,000 nucleotides that included 20 genes, they carefully scanned 19 of them before finding a mutation in the very last one; it was a small, two-base pair insertion that threw the coding out of frame and resulted in a stunted protein. The mutated gene hadn't been studied before, but it looked like others that were classified as forkhead/winged-helix genes, so Brunkow and Ramsdell called it Foxp3."

"The pair then did genetic rescue experiments, putting normal Foxp3 genes back into scurfy mice-doing it in five lines, for good measure. The genetic rescue prevented the severe autoimmune 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 humans, called IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked). IPEX causes a fatal autoimmune disease in young boys."

Researchers narrowed an X-chromosome mutation to a 500,000-nucleotide region containing 20 genes and found a two-base-pair insertion in the Foxp3 gene that caused a frameshift and produced a stunted protein. Restoring normal Foxp3 in scurfy mice prevented severe autoimmune disease, confirming the mutation as causal. Mutations in human FOXP3 were linked to IPEX, a fatal early-onset autoimmune syndrome in boys. Foxp3 expression is selectively induced in regulatory T cells, and ectopic Foxp3 converts helper T cells into regulatory cells. Foxp3 functions as a master transcriptional regulator that enables T cells to enforce peripheral immune tolerance.

Read at Ars Technica