Front. Immunol., 19 September 2013 | doi: 10.3389/fimmu.2013.00291
- 1Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, Newark, NJ, USA
- 2Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
Patients with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) display increased levels of type I interferon (IFN)-induced genes. Plasmacytoid dendritic cells (PDCs) are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN-inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes – those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K) pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell-type specific gene signatures as well as identify distinct transcription factors (TFs) that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of theIFNA and IFNB genes are occupied by TFs, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as interferon regulatory factor (IRF)5 and IRF7, that positively and distinctly regulateIFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.
Keywords: type I interferons, bioinformatics, autoimmunity, transcriptional regulation, transcription, genetic
Citation: Feng D and Barnes BJ (2013) Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity. Front. Immunol. 4:291. doi: 10.3389/fimmu.2013.00291
Received: 19 June 2013; Accepted: 04 September 2013;
Published online: 19 September 2013.
Published online: 19 September 2013.
Edited by:
Timothy B. Niewold, Mayo Clinic, USA
Reviewed by:
Devendra K. Agrawal, Creighton University School of Medicine, USAMin Wu, University of North Dakota, USA
Copyright: © 2013 Feng and Barnes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Di Feng, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, 205 South Orange Avenue, Newark, NJ 07103, USA e-mail: fengdi@njms.rutgers.edu
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