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!
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy