Am J Transl Res 2012;4(2):219-228 www.ajtr.org /ISSN:1943-8141/AJTR1202002 Original Article Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation Aik T Ooi1, Sonal Ram1, Alan Kuo1, Jennifer L Gilbert1, Weihong Yan2, Matteo Pellegrini3, Derek W Nickerson1, Talal A Chatila4, Brigitte N Gomperts1,5,6,7 1David Geffen School of Medicine at UCLA, Department of Pediatrics, Mattel Children's Hospital, Los Angeles, CA 90095, USA; 2Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095 USA; 3Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, 90095 USA; 4Division of Immunology, The Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston MA 02115; 5David Geffen School of Medicine at UCLA, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Los Angeles, CA 90095, USA; 6Broad Stem Cell Research Center at UCLA, Los Angeles, CA, 90095, USA; 7Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, 90095, USA Received February 12, 2012; accepted March 22, 2012; Epub April 10, 2012; Published April 30, 2012 Abstract: Epigenetic changes have been implicated in the pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and remodeling, induced epigenetic DNA methylation and miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. Inducible expression of an IL13 trans-gene in the airways resulted in significant changes in DNA methylation in 177 genes, most of which were associated with the IL13 transcriptional signature in the airways. A large number of genes whose expression was induced by IL13 were found to have decreased methylation, including those involved in tissue remodeling (Olr1), leukocyte influx (Cxcl3, Cxcl5, CSFr2b), and the Th2 response (C3ar1, Chi3l4). Reciprocally, some genes whose expression was sup-pressed were found to have increased methylation (e.g. Itga8). In addition, miRNAs were identified with targets for lung development and Wnt signaling, amongst others. These results indicate that IL13 confers an epigenetic methyla-tion and miRNA signature that accompanies its transcriptional program in the airways, which may play a critical role in airway inflammation and remodeling. Keywords: Epigenetics, miRNA, DNA methylation, allergic airway disease