Modifications in the lung DNA methylation landscape in a murine model of respiratory allergy induced by two Blomia tropicalis allergens

Abstract

Allergic asthma is caused by the interplay between genetic and environmental factors. Among the latter, allergens from house dust mites, including Blomia tropicalis, are the main inductors of this disease. Upon inhalation, these molecules cause allergic inflammation in the lungs of genetically- and epigenetically predisposed individuals. In addition, they can influence the epigenetic mechanisms of gene expression regulation in the airways. However, the epigenetic effects of individual mite allergens and their role in asthma pathogenesis have not yet been explored. Research on this topic is scarce, and only whole extracts of Dermatophagoides spp. have been used. In this study, we evaluated the modifications in the mouse lung methylome induced by two individual allergens (Blo t 2 and Blo t 13) and the whole extract of Blomia tropicalis (a mite particularly abundant in tropical and subtropical regions) and their association with allergic airway inflammation measures. Using a microarray-based DNA methylation analysis method and robust bioinformatic analyses, including principal component-adjusted linear regression, we found that exposure to these allergens modified the mouse lung methylome and identified several differentially methylated positions and regions. Genes associated with these DNA methylation changes were enriched for key biological functions, including cell-cell adhesion, immune response, and various cell signaling pathways. In addition, the methylation levels of some of these sites correlated with measures of allergic airway inflammation. This is the first report of changes in the DNA methylation induced by Blomia tropicalis extract and two of its allergens, thus contributing to the characterization of the allergenic activity of these molecules. The implicated genes and biological pathways are important for the pathogenesis of allergic asthma and mechanisms of the inflammatory response to inhaled allergens