Immune-Mediated Pulmonary Disease and Epigenetics

Abstract Asthma and pulmonary arterial hypertension (PAH) are lung diseases that share the common feature of sterile inflammation, which contributes to remodeling of the airways and pulmonary vasculature. In both lung pathologies, disease-initiating events increase the infiltration of immune-system cells into lung tissues and the number of resident immune cells expands in the walls of airways and blood vessels. In asthma, the immune-cell content of airway secretions also increases. Each immune cell type (i.e., lymphocytes, monocytes, macrophages, dendritic cells, eosinophils, and mast cells) responds by migrating to the site of the insult and either proliferating, or more commonly secreting a diverse set of small-molecule mediators. The chemical and mechanical cues that promote airway and vascular inflammation often lead to changes in gene expression, which are determined by epigenetic factors. DNA methylation, histone modifications, and noncoding RNAs can finely tune the inflammatory response. The type and extent of inflammation varies depending on the subject's genetic background and the biochemical milieu of the responding cells. This review will focus on two airway diseases that show significant type II inflammation that is regulated by epigenetic mechanisms. Defining the epigenetic regulation of lung inflammation is the first step towards identifying novel therapeutic targets. Identifying novel drug targets will address an unmet need for steroid-resistant asthma and PAH, both of which are treated ineffectively using current drugs.