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Page: << Prev | 1 | 2 They focused on a protein that is found only in regulatory T-cells, called Foxp3. Foxp3 is a transcription factor -- that is, it dials up or down the production of other genes. Its significance in controlling the immune system is underscored by the fact that people with mutant Foxp3 genes develop IPEX, a syndrome marked by massive autoimmune disorders and early mortality.
Using sophisticated gene microarray technology, the team scanned the entire T-cell genome. "We identified a set of roughly 30 genes that are clearly regulated by Foxp3 and, surprisingly, a lot of them are suppressed by Foxp3," said study lead author Alexander Marson, a graduate student at Harvard Medical School and MIT.
These targets, "are probably essential to give regulatory T-cells their unique function," and include genes that have previously been implicated in immune regulation, Marson said. Mutation in one of these down-regulated genes, Ptpn22, is associated with a number of autoimmune disorders.
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Marson said the work has at least two significant implications for research. "One is that we've identified this core set of genes that are probably likely to play key roles in preventing autoimmune disease," he said. "The second implication, which is maybe more long-term, is that we hope that identifying these targets will allow us to screen for drugs to mimic the function of Foxp3 and thus treat autoimmune disease."
According to Rose, treating autoimmune disorders will require enhancing either the number or effectiveness of regulatory T-cells.
"There are some tricks we might be able to use for both of those," he said. Rose also sees applications in transplant medicine and in the fight against cancer.
"Interestingly, people interested in tumor immunology are also interested in regulatory T-cells, because if you can get them out of the way, you can get rid of the tumor," he said.
Rose stressed that it remains to be seen which, if any, of these genes would make good drug targets. But he expressed confidence in the clinical potential of regulatory T-cells. "They have enormous implications, if we can figure out how to make them do what we want them to do."
More information
For more on how the immune system works, head to the American College of Rheumatology.
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