AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Transl Res 2012;4(2):219-228

Original Article
Identification of an interleukin 13-induced epigenetic signature in
allergic airway inflammation

Aik T Ooi, Sonal Ram, Alan Kuo, Jennifer L Gilbert, Weihong Yan, Matteo Pellegrini, Derek W Nickerson, Talal A
Chatila, Brigitte N Gomperts

David Geffen School of Medicine at UCLA, Department of Pediatrics, Mattel Children’s Hospital, Los Angeles, CA
90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095 USA;
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, 90095 USA;
Division of Immunology, The Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston
MA 02115; David Geffen School of Medicine at UCLA, Department of Medicine, Division of Pulmonary and Critical
Care Medicine, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center at UCLA, Los Angeles, CA,
90095, USA; Jonsson 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 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 transgene 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 suppressed 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 methylation and miRNA signature that accompanies its
transcriptional program in the airways, and which may play a critical role in airway inflammation and remodeling.

Keywords: Epigenetics, miRNA, DNA methylation, allergic airway disease

Address all correspondence to:
Dr. Brigitte N. Gomperts
David Geffen School of Medicine at UCLA
Department of Pediatrics
10833 Le Conte Ave., A2-410MDCC
Los Angeles, CA 90095, USA.
Tel: (310) 825-6708
E-mail: bgomperts@mednet.ucla.edu