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 Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>