Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study points to key genetic driver of severe allergic asthma

30.08.2010
Scientists have identified a genetic basis for determining the severity of allergic asthma in experimental models of the disease.

The study may help in the search for future therapeutic strategies to fight a growing medical problem that currently lacks effective treatments, researchers from Cincinnati Children's Hospital Medical Center report in the Aug. 29 Nature Immunology.

The prevalence of asthma has been increasing in recent years, according to Marsha Wills-Karp, Ph.D., director of the division of Immunobiology at Cincinnati Children's and the study's senior investigator. The disease can be triggered in susceptible people by a variety of environmental contaminants – such as cigarette smoke, allergens and airborne pollution.

Dr. Wills-Karp's research team has found a molecular tipping point that upsets a delicate balance between underlying mild disease and more severe asthma. They identify the pro-inflammatory protein, interleukin-17 (IL-17A), as the chief culprit behind severe asthma-like symptoms in mice.

"This study suggests that at some point it may be possible to treat or prevent severe forms of asthma by inhibiting pathways that drive the production of IL-17A," Dr. Wills-Karp said.

The disease process appears to begin when airway exposure to environmental allergens causes dysfunctional regulation of a gene called complement factor 3 (C3), which works through a part of the immune system called the complement activation cascade. This leads to overzealous production of IL-17A by airway cells and sets off what the scientists describe as an "amplification loop," when IL-17A in turn induces more C3 production at the airway surface.

The amplification loop perpetuates increasing inflammatory responses involving irregular T helper cells, other interleukin proteins (IL-13 and IL-23), as well as airway hyper-responsiveness and airflow obstruction.

Previous studies have shown the presence of IL-17A proteins in human asthma but no apparent role. Earlier research involving mouse models of the disease has suggested possible roles for IL-17A in asthma, and this study expands on those findings.

The current study involved mice bred genetically to closely resemble people susceptible to severe asthma. Mouse airways were exposed to house dust mite allergen extract to gauge the severity of disease and analyze biochemical responses in airway tissues.

One group of mice was deficient in the immune system gene C5, which normally prevents harmful airway immune responses to inhaled environmental allergens. These mice generated high numbers of T helper cells (known specifically in this instance as TH17 cells) that produced significant IL-17A and caused airway hyper-responsiveness. When researchers blocked IL-17A production in this group, the mice had less airway hyper-responsiveness.

A second group of mice was deficient in the C3aR gene (a receptor for C3), which regulates the dysfunctional response to airway allergens that lead to asthma. These mice had fewer IL-17A producing TH17 cells and less airway hyper-responsiveness. When researchers increased the amount of IL-17A in the airways of this group, the mice experienced greater airway hyper-responsiveness.

As Dr. Wills-Karp and her colleagues continue their research, they will study the relationship between C3 and IL-17A in severe asthmatics, and explore the effectiveness of targeting either the C3 or IL-17A pathways for the treatment of severe asthma. A drug that blocks the function of C3 is currently under development and testing outside of Cincinnati Children's for treatment of the eye disease macular degeneration.

Funding support for the study came from the National Institutes of Health and the Parker B. Francis Fellowship Program.

Also collaborating on the study were co-first authors Stephane Lajoie, Ph.D., and Ian Lewkowich, Ph.D., research fellows in Dr. Wills-Karp's laboratory.

About Cincinnati Children's

Cincinnati Children's Hospital Medical Center is one of just eight children's hospitals named to the Honor Roll in U.S. News and World Report's 2010-11 Best Children's Hospitals. It is ranked #1 for digestive disorders and highly ranked for its expertise in pulmonology, cancer, neonatology, heart and heart surgery, neurology and neurosurgery, diabetes and endocrinology, orthopedics, kidney disorders and urology. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for quality and transformation work by Leapfrog, The Joint Commission, the Institute for Healthcare Improvement, the federal Agency for Healthcare Research and Quality, and by hospitals and health organizations it works with globally. Additional information can be found at www.cincinnatichildrens.org.

Nick Miller | EurekAlert!
Further information:
http://www.cchmc.org
http://www.cincinnatichildrens.org

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Creating a new composite fuel for new-generation fast reactors

20.06.2018 | Materials Sciences

Game-changing finding pushes 3D-printing to the molecular limit

20.06.2018 | Materials Sciences

Could this material enable autonomous vehicles to come to market sooner?

20.06.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>