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Dartmouth researchers find key player in immune system regulation

HANOVER, NH Studies led by Dartmouth Medical School researchers have revealed a crucial link in how the immune system works. In a study published online on August 20 in the journal Nature, the researchers found that mast cells, known for their role in allergy reactions such as watery eyes and runny noses, are connected to the activity of regulatory T cells, which suppress immune responses. The researchers say theirs is the first study to find that mast cells mediate immune system suppression.

"Our finding is a complete surprise. We were studying transplant tolerance and what's required to protect a graft from rejection," says Randolph Noelle, professor of microbiology and immunology at Dartmouth Medical School. "When we went looking to see what genes were responsible in a successful graft, we found high levels of mast cell gene products, which made the connection between regulatory T cells and mast cell recruitment. The fact that mast cells may be instrumental in orchestrating regulatory T cell tolerance was new, unanticipated, and surprising."

In their study, the researchers determined that mast cells are crucial for sustaining immune suppression in transplanted skin on mice, which means longer acceptance or tolerance of the transplant. Mice that were mast cell deficient rejected the skin graft. Furthermore, the researchers found that IL-9, a protein already known for playing a role in mast cell activation and recruitment, was discovered to be produced by regulatory T cells. As such, the other key discovery in this study was that Il-9 appears to be an essential ingredient in the success of transplanted skin.

"Because of this study, mast cells are now the new cellular target in understanding immune suppression," says Noelle, who is co-director of the Immunotherapy Program of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center. "We now have a whole new set of cellular, and eventually molecular, interactions to stu
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Contact: Sue Knapp
Sue.Knapp@Dartmouth.edu
603-646-3661
Dartmouth College
24-Aug-2006


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