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!
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy