• Discovery may lead to new treatments for allergic diseases

    Researchers from Cincinnati Children’s and Tel Aviv University in Israel have discovered a molecular pathway that has broad implications for treating eosinophil-associated disorders.

    Eosinophils are normal cellular components of blood, but when the body produces too many eosinophils it can cause chronic inflammation resulting in tissue damage, often in the gastrointestinal system. Eosinophils are regulated by interleukin 5 (IL-5), a protein that triggers them to leave the bone marrow and enter the bloodstream.

    The new research identifies a pathway for counterbalancing what happens when IL-5 triggers eosinophils. The study is published online in the journal Nature Immunology.

    "The fundamental knowledge we have gained may one day yield new therapies to treat devastating eosinophilic disorders," says Ariel Munitz, PhD, a researcher at the Sackler School of Medicine at Tel Aviv University and corresponding author of the study.

    Munitz and Marc Rothenberg, MD, PhD, director of Allergy and Immunology at Cincinnati Children's, report that the newly identified pathway involves a pair of proteins, PIR-A and PIR-B, that play a critical role in eosinophil development. PIR-A induces eosinophils to die but PIR-B inhibits its actions. For PIR-A to keep eosinophil production in check, PIR-B must be shut down.

    Asthmatic mice bred to lack PIR-B had little expansion of eosinophils in their blood and less asthmatic inflammation in their lungs than normal mice. This finding indicates that inflammation might be better controlled by enhancing PIR-A or weakening PIR-B so that it inhibits PIR-A to a lesser extent.

    The study is part of the Israel Exchange Program (IEP) at Cincinnati Children's, a collaborative effort with leading Israeli institutions to improve clinical care, train clinicians and researchers and accelerate development of technological breakthroughs that benefit children.

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    Marc Rothenberg, MD, PhD, director of Allergy and Immunology at Cincinnati Children's Hospital.

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