Epigenetic mechanisms through which Toll-like receptor-9 drives idiopathic pulmonary fibrosis progression.

Patients with idiopathic pulmonary fibrosis (IPF) survive a median of 3 years after diagnosis, but a high degree of variability in longitudinal disease progression has been observed. Unfortunately, physiology and clinical parameters determined at the time of diagnosis have proven inaccurate in predicting the rate at which IPF ultimately progresses. A mechanistic explanation for disease progression in patients with IPF is presently unclear, but we have recently shown that hypomethylated CpG DNA drives the rapid progression of fibrotic lung disease through the differentiation of pulmonary fibroblasts into myofibroblasts through a TLR9-dependent mechanism. Furthermore, we recently reported that the clinical progression of IPF might be a consequence of aberrant microRNA processing. Using this framework of data, we are presently addressing the following specific hypothesis: hypomethylated CpG DNA activation in pulmonary fibroblasts leads to aberrant micro RNA processing, thereby promoting the rapid progression of IPF.