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2 genes are important key to regulating immune response
Date:12/28/2007

h, that can help encourage AIDS in those infected with HIV. Also, excessive T-cell suppression can keep the immune system from destroying rogue cancer cells in people battling malignancy."

All of this means that "anything that we can learn about IL-10 production -- and related T-cell suppression -- is a boon to medical research," Dr. Ma explains.

Prior studies had already shown that CD36 -- a protein receptor lying on the surface of the macrophage -- was important for the recognition of apoptotic cells by macrophages. In this work, the researchers observed that CD36 also helped to trigger IL-10 production whenever apoptotic cells were around.

The team then asked a deeper question: "What signals lead to IL-10 production from CD36 present at the cell surface""

To find out, the Weill Cornell group first exposed macrophages to apoptotic (dying) cells. They then used sensitive assays to look for key biochemical changes occurring downstream of CD36 activation.

"We found proteins in the cell nucleus that were binding to a site we knew was critical for the production of IL-10 as macrophages encountered apoptotic cells," Dr. Ma says. In subsequent biochemical experiments, the team identified the two genes responsible for the transcription (gene-directed production) of these proteins.

These genes -- pre-B transcription factor 1(Pbx-1) and Pbx-regulating protein 1 (Prep-1) -- are best known to scientists as partners for their role in embryonic development and several forms of leukemia, with Pbx playing a major part in hematopoeisis, the production of new and myriad blood cell types.

"In that sense, their presence as immune system transcription factors came as a big surprise to us," Dr. Ma says. "In fact, we still haven't figured out exactly how Pbx-1 and Prep-1 are involved in regulating IL-10 transcription. I really hope this study opens up new avenues for immunologists to find out whether there's a brand ne
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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