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Putting the brakes on immunity
Date:11/12/2013

rious organs. IL-5 has lately been investigated as a new target for asthma medications, some of which have proven effective in clinical trials.

Analyzing the bone marrow of mice, the researchers found that the expansion of eosinophils caused by IL-5 is actually part of a broader mechanism that regulates the lifecycle of the cells. While IL-5 commands eosinophils to expand and enter the bloodstream, a cell receptor called paired immunoglobulin-like receptor A, or PIR-A, commands eosinophils to die. So eosinophils are in a constant "tug of war" between survival signals delivered by IL5 and death orders delivered by PIRA.

Although the death order by PIR-A is dominant, it is never executed. Eosinophils express another receptor, called PIR-B, which closely resembles PIR-A and inhibits its actions. In order for PIR-A to carry out its death order to the cell, PIR-B must be shut down.

"PIR-A is always inhibited by PIR-B from the very early stages of eosinophil development," says Dr. Munitz. "We had to remove the expression of PIR-B from the cells to see PIR-A's powerful effects."

Two new approaches to nip disease in the bud

After identifying the mechanism in cell culture systems, the researchers verified that it also operates in mice. As expected, they found that asthmatic mice without PIR-B in their bodies had very little expansion of eosinophils into their blood and lungs and therefore less asthmatic inflammation in their lungs than normal mice. Unhindered by PIR-B, PIR-A appeared to keep eosinophils from reaching harmful levels in their bodies. Because human eosinophils also express PIR-like molecules, there is good reason to believe the same mechanism works in people.

In addition to advancing knowledge of eosinophils a basic and important cell type the researchers' work opens up two new avenues for treating eosinophilic disorders. Instead of lowering IL-5 levels to try to reduce eosinophil expansion, scienti
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Contact: George Hunka
ghunka@aftau.org
212-742-9070
American Friends of Tel Aviv University
Source:Eurekalert

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