The prevalence of allergic asthma rised significantly in the last 50 years. Epidemiological studies have shown that this trend might be caused by lifestyle changes in the Western world and by a reduction in the incidence of infectious diseases. Conversely, growing up on a farm or in a house with high endotoxin in the home environment has been shown to offer protection from allergy.
How these factors can influence the development of asthma, a disorder where Th2 cells play a big role, has been an enigma. Most explanations have centered around a disordered balance in the immune system, with a decrease in Th1 and/or Tregs in the absence of infectious pressure from the environment leading to an increase in Th2 responses. In this project, we take a fresh look and we propose that the increase in allergic diseases is due to altered function of airway epithelial cells. In the past years, we have shown that lung epithelial cells are not only a physical barrier, but play an important role in the sensitization to allergens by activating airway dendritic cells. Pilot experiments have shown that environmental endotoxin exposure protects from the development of asthma via inducing a molecule that suppresses innate immunity in epithelial cells. In this
project, we will study how exactly endotoxin reprograms epithelial cells to suppress asthma. We will translate our findings to human using epithelial cell-brushes and human cell lines, to compare asthmatics versus healthy patients.