The researchers from Tel Aviv University and Cincinnati Children's Hospital Medical Center have discovered how this pathway kills eosinophils before they can cause havoc.
Eosinophils are normal cellular components of the blood, but when the body produces too many eosinophils they can cause a variety of eosinophilic disorders. These are disorders involving chronic inflammation resulting in tissue damage, often in the gastrointestinal system.
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 department of Clinical Microbiology and Immunology at the Sackler School of Medicine at Tel Aviv University and corresponding author of the study.
Eosinophils are regulated by interleukin 5 (IL-5), a protein that triggers eosinophils to leave the bone marrow and enter the bloodstream, where they can reach various organs. Dr. Munitz and Marc Rothenberg, MD, PhD, director of Allergy and Immunology at Cincinnati Children's, have identified a pathway for counterbalancing what happens when IL-5 triggers eosinophils. The newly identified pathway involves a key checkpoint controlled by a pair of proteins, PIR-A and PIR-B, which the researchers now show have a critical role in eosinophil development.
PIR-A induces eosinophils to die and thus is in a perpetual tug-of-war with survival and growth signals driven by IL-5. The researchers discovered that PIR-A is dominant in this battle but that cell death doesn't occur because PIR-B inhibits its actions. For PIR-A to win the battle and cause cells to die, PIR-B must be shut down.
The researchers studied asthmatic mice and discovered that asthmatic mice without PIR-B had little expansion of eosinophils in their blood and lungs and less asthmatic inflammation in their lungs than normal mice. The lack of PIR-B kept eosinophils from reaching harmful levels. The researchers hope that scientists can now target PIR-A to enhance its ability to kill eosinophils or weaken PIR-B so that it inhibits PIR-A to a lesser extent.
The study was led by Netali Baruch-Morgenstern and Dana Shik from the Munitz lab. They are graduate students at Tel Aviv University who spent part of their training in Dr. Rothenberg's lab at Cincinnati Children's. Dr. Munitz is a former research fellow in Dr. Rothenberg's lab.
The study was funded in part by a grant from the United States-Israel Binational Science Foundation (grant number 2009222), which promotes scientific relations between the U.S. and Israel by supporting collaborative research projects in a wide area of basic and applied scientific fields.
Funding also came from the FP7 Marie-Curie Reintegration grant (grant number 256311), the Israel Science Foundation (grant numbers 955/11 and 1708/11), the Israel Cancer Research Foundation Research Career Development Award, the Fritz Thyssen Foundation, the US-Israel Bi-national Science Foundation, the National Institute of Allergy and Infectious Diseases, (R01AI083450, R37AI045898), CURED Foundation, FARE, and Buckeye Foundation.
The study also is the result of the Israel Exchange Program (IEP) at Cincinnati Children's. The IEP is a collaboration with leading Israeli institutions to improve clinical care for children, train pediatric providers and researchers, advance scientific research and make technological breakthroughs that benefit children throughout the world. Collaborations include Israeli and Cincinnati Children's physicians jointly treating patients with complex conditions in Cincinnati and Israel; clinical and research postdoctoral fellowships at Cincinnati Children's for Israelis; short-term training opportunities at Cincinnati Children's for Israeli physicians, nurses, students, paraprofessionals and hospital administrators; grants to support collaborative research; co-sponsorship of conferences and research symposia in Israel and Cincinnati; and technology collaborations with Israeli start-ups and universities.
Munitz lab: http://www.tau.ac.il/~arielm/Ariel_Munitz,_PhD/Welcome.html
Rothenberg lab: http://www.cincinnatichildrens.org/research/divisions/a/allergy-immunology/labs/rothenberg/default/
Rothenberg lab Facebook page: http://www.facebook.com/RothenbergEosinophilicLab
Cincinnati Center for Eosinophilic Disorders: http://www.cchmc.org/cced
Israel Exchange Program: http://www.cincinnatichildrens.org/service/g/global/israel/default/
About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S.News and World Report's 2013 Best Children's Hospitals ranking. It is ranked #1 for cancer and in the top 10 for nine of 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.
Nick Miller | EurekAlert!
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy