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!
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering