Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

Patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) display increased levels of type I 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. Diffe...

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Main Authors: Di eFeng, Betsy eBarnes
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00291/full
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author Di eFeng
Di eFeng
Betsy eBarnes
Betsy eBarnes
author_facet Di eFeng
Di eFeng
Betsy eBarnes
Betsy eBarnes
author_sort Di eFeng
collection DOAJ
description Patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) display increased levels of type I 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 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 the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA 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.
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spelling doaj.art-0a99ca69c705401ca11857acc87ae79d2022-12-22T00:52:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-09-01410.3389/fimmu.2013.0029159907Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunityDi eFeng0Di eFeng1Betsy eBarnes2Betsy eBarnes3Rutgers Biomedical and Health SciencesRutgers Biomedical and Health SciencesRutgers Biomedical and Health SciencesRutgers Biomedical and Health SciencesPatients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) display increased levels of type I 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 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 the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00291/fullAutoimmunityTranscription, GeneticbioinformaticsTranscriptional regulationType I Interferons
spellingShingle Di eFeng
Di eFeng
Betsy eBarnes
Betsy eBarnes
Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
Frontiers in Immunology
Autoimmunity
Transcription, Genetic
bioinformatics
Transcriptional regulation
Type I Interferons
title Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
title_full Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
title_fullStr Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
title_full_unstemmed Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
title_short Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity
title_sort bioinformatics analysis of the factors controlling type i ifn gene expression in autoimmune disease and virus induced immunity
topic Autoimmunity
Transcription, Genetic
bioinformatics
Transcriptional regulation
Type I Interferons
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00291/full
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