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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.
Randy Noelle (center) and members of his laboratory, clockwise: Cory Ahonen,
Victor Devries, Evan Lind, Micah Benson, Anna Wasiuk, Zach Scott, and Dave
Gondek. (Photo by Joseph Mehling '69)
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"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 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.
"Mast cells are now the new cellular target in understanding immune
suppression," says Noelle, who is codirector 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 study."
According to Noelle, the findings might also impact some cancer treatments
as mast cells are known to promote growth in some tumors. Future research might
look into suppressing mast cells to boost the immune system, which could lead
to tumor rejection.
"It is only because of the extremely high quality of the graduate
students in Dartmouth's molecular and
cell biology program and the hard work of postdoctoral fellows and
colleagues that this new paradigm of cellular interactions in immunology was
discovered," says Noelle.
Collaborating researchers on this study include Li-Fan Lu, Evan Lind, David
Gondek, Kathy Bennett, Michael Gleeson, Karina Pino-Lagos, and Zachary Scott,
all at Dartmouth; Anthony Coyle and Jennifer Reed at MedImmune in Gaithersburg,
Md.; Jacques Van Snick at the Ludwig Institute for Cancer Research at the
University of Louvain in Brussels, Belgium; and Terry Strom and Xin Zheng at
Beth Israel Deaconess Medical Center in Boston, Mass.
Noelle's research is funded by the National
Institutes of Health.
By SUSAN KNAPP
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