Featured Research

from universities, journals, and other organizations

Study points to key genetic driver of severe allergic asthma

Date:
August 31, 2010
Source:
Cincinnati Children's Hospital Medical Center
Summary:
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 report.

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.


Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Stephane Lajoie, Ian P Lewkowich, Yusuke Suzuki, Jennifer R Clark, Alyssa A Sproles, Krista Dienger, Alison L Budelsky & Marsha Wills-Karp. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nature Immunology, 2010; DOI: 10.1038/ni.1926

Cite This Page:

Cincinnati Children's Hospital Medical Center. "Study points to key genetic driver of severe allergic asthma." ScienceDaily. ScienceDaily, 31 August 2010. <www.sciencedaily.com/releases/2010/08/100829201950.htm>.
Cincinnati Children's Hospital Medical Center. (2010, August 31). Study points to key genetic driver of severe allergic asthma. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2010/08/100829201950.htm
Cincinnati Children's Hospital Medical Center. "Study points to key genetic driver of severe allergic asthma." ScienceDaily. www.sciencedaily.com/releases/2010/08/100829201950.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins