Title Regulation of IFN-lambda1 promoter activity (IFN-lambda1/IL-29) in human airway epithelial cells.
Author Siegel, Rachael; Eskdale, Joyce; Gallagher, Grant
Journal J Immunol Publication Year/Month 2011-Dec
PMID 22058416 PMCID -N/A-
Affiliation 1.Genetic Immunology Laboratory, HUMIGEN LLC, Institute for Genetic Immunology, Genesis Biotechnology Group, Hamilton, NJ 08690, USA.

The type III (lambda) IFNs (IFN-lambda1, IFN-lambda2, and IFN-lambda3) and their receptor are the most recently discovered IFN family. They are induced by viruses and mediate antiviral activity, but type III IFNs have an important, specific functional niche at the immune/epithelial interface, as well as in the regulation of Th2 cytokines. Their expression appears diminished in bronchial epithelial cells of rhinovirus-infected asthmatic individuals. We investigated the regulation of IFN-lambda1 expression in human airway epithelial cells using reporter genes analysis, chromatin immunoprecipitation, small interfering RNA knockdown, and DNase footprinting. In this article, we define the c-REL/p65 NF-kappaB heterodimer and IRF-1 as key transcriptional activators and ZEB1, B lymphocyte-induced maturation protein 1, and the p50 NF-kappaB homodimer as key repressors of the IFN-lambda1 gene. We further show that ZEB1 selectively regulates type III IFNs. To our knowledge, this study presents the first characterization of any type III IFN promoter in its native context and conformation in epithelial cells and can now be applied to understanding pathogenic dysregulation of IFN-lambda1 in human disease.

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