Researchers at Washington University School of Medicine in St. Louis have received an $8 million grant from the National Institutes of Health (NIH) to study the role of the barrier functions of the skin, gut and airway in asthma and allergic diseases.
Understanding the role of the epithelial cells in these tissues may help prevent and treat respiratory illnesses in the future, the researchers say.
“The epithelial cells are critical for forming a barrier between the organism and its environment,” says principal investigator Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine. “The reaction of these cells to the environment can determine whether the host develops a normal immune response or an inflammatory disease process. We want to figure out how these reactions might move in a helpful direction and provide protection against the environment or in a harmful direction, leading to inflammatory diseases such as asthma.”
Toward this goal, the grant supports three projects:
- The first project investigates how airway epithelial cells use proteins called “interferons” to protect against viral infection. Holtzman and his colleagues demonstrated that viral infections could lead to the development of asthma. They are now developing methods to enhance the efficiency of the interferon system as a means to protect against respiratory viruses and prevent the development of asthma.
- The second project studies how airway epithelial cells get converted to overproduce mucus in the airways, a major cause of illness and death in patients with asthma and allergic disease. The researchers learned that special proteins involved with autophagy, the recycling of old cellular parts, also regulate mucus formation in gut epithelial cells. They will now study whether these proteins also regulate airway mucus as a means of controlling this process in asthma.
- The third project explores how epithelial cells in the skin might contribute to asthma. The researchers learned that damage to epithelial cells in the skin leads to a condition similar to atopic dermatitis and, in turn, an asthma-like condition. This “atopic march” also occurs in children, so this project aims to understand and interrupt this process as a means to prevent asthma.
“In combination, we are investigating the broad role of the epithelial barrier in the development of inflammatory airway disease,” Holtzman says. “The center is unified around a goal of understanding how the epithelial barrier normally protects us but abnormally causes a remarkably common and serious type of disease. The approach is designed to use that information to preserve or restore the epithelial balance with the environment.”
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.