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Dartmouth researchers find key player in immune system regulation

Dartmouth College Office of Public Affairs • Press Release

Posted 08/24/06 • Knapp

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.

Randolph Noelle and researchers

Randy Noelle, center, and members of his laboratory, clockwise: Cory

Ahonen, Victor Devries, Evan Lind, Micah Benson, Wasiuk, Zach

, and Dave Gondek. (Photo by ph Mehling '69)

" 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 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 post-docs 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,

Gondek, Kathy , Gleeson, Karina Pino-Lagos, and

Zachary , all at Dartmouth; Coyle and 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.

http://www.dartmouth.edu/~news/releases/2006/08/24.html

Dartmouth researchers find key player in immune system regulation

Dartmouth College Office of Public Affairs . Press Release Posted

08/24/06 . Knapp 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. Randolph Noelle and

researchers Randy Noelle, center, and members of his laboratory,

clockwise: Cory Ahonen, Victor Devries, Evan Lind, Micah Benson,

Wasiuk, Zach , and Dave Gondek. (Photo by ph Mehling '69)

" 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

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

post-docs 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, Gondek,

Kathy , Gleeson, Karina Pino-Lagos, and Zachary ,

all at Dartmouth; Coyle and 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 Me