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Gene expression data: Plasmacytoid dendritic cells (pDCs) of healthy donors and MS patientes before and after IFN beta treatment

ABSTRACT: Multiple Sclerosis (MS) is an immune-mediated chronic inflammatory disease affecting the central nervous system. The cause of MS is not known and the mechanism of IFN-beta, a disease-modifying treatment (DMT) approved for MS, is not well-understood. Oligonucleotide microarrays were used to study gene expression in plasmacytoid denditic cells (pDCs) which are antigen-presenting cells implicated in MS pathogenesis. We analyzed gene expression in pDCs of healthy controls, untreated and IFN-beta treated MS patients. We were able to identify 60 genes which were abnormally expressed in untreated MS patients and were corrected after treatment with IFN-beta.

ORGANISM(S): Homo sapiens

PROVIDER: GSE37750 | GEO | 2015/05/02

SECONDARY ACCESSION(S): PRJNA163239

REPOSITORIES: GEO

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Gene expression data: Plasmacytoid dendritic cells (pDCs) of healthy donors and MS patientes before and after IFN beta treatment

Project description:Multiple Sclerosis (MS) is an immune-mediated chronic inflammatory disease affecting the central nervous system. The cause of MS is not known and the mechanism of IFN-beta, a disease-modifying treatment (DMT) approved for MS, is not well-understood. Oligonucleotide microarrays were used to study gene expression in plasmacytoid denditic cells (pDCs) which are antigen-presenting cells implicated in MS pathogenesis. We analyzed gene expression in pDCs of healthy controls, untreated and IFN-beta treated MS patients. We were able to identify 60 genes which were abnormally expressed in untreated MS patients and were corrected after treatment with IFN-beta. PDCs were separated from healthy donors and MS patients at two time points: before and 3 months after initiation of treatment with IFN-beta for RNA extraction and hybridization on Affymetrix microarrays. Gene expression data analysis of was done by GeneSpring software (Agilent Technologies). An unpaired t-test was applied to select genes with significant difference in expression between healthy donors and untreated MS patients. A paired t-test was applied to select genes with significant difference in expression in MS patients before and after IFN-beta treatment. To select differentially expressed/regulated genes, the cut-off criteria consisted of a P value < 0.05 and fold change >1.5.

2015-05-02 | E-GEOD-37750 | biostudies-arrayexpress

TLR-mediated type I IFN induction in pDCs requires the rapamycin-sensitive PI3K-mTOR-p70S6K pathway

Project description:Robust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the ‘downstream’ mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs. CpGA is a TLR9 agonist. pDCs were isolated from mouse spleen or human PBMC. The effect of rapamycin on pDCs IFN-alpha production as induced by TLR ligands was studied. The mechanism of rapamycin effect was dissected in RAW cell line.

2008-12-01 | E-GEOD-12218 | biostudies-arrayexpress

Proteomic and single-cell transcriptomic dissection of human plasmacytoid dendritic cell response to influenza virus

Project description:Plasmacytoid dendritic cells (pDCs) represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons (IFN-I). This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in response to challenge with live influenza H1N1. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversification following stimulation. Our data reveal an abundance of protein species released by pDCs in addition to IFN-I, and evidence highly specialized roles within the pDC population ranging from dedicated cytokine super-producers to cells with APC-like functions. Moreover, dynamic expression of transcription factors and surface markers characterize activated pDC fates.

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Search for specific biomarkers of IFN-beta bioactivity in patients with MS

Project description:We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis. Number of samples: 32. We analyzed PBMC from 8 patients at baseline and after 3, 12 and 24 months of IFN-beta treatment

2010-12-18 | E-GEOD-26104 | biostudies-arrayexpress

Search for specific biomarkers of IFN-beta bioactivity in patients with MS

2010-12-18 | GSE26104 | GEO

Single-cell analysis of mouse plasmacytoid dendritic cells (pDCs) unravels their activation trajectory and their molecular regulation in vivo during a viral infection [Ss2_pDC1]

Project description:The aim of the project is to characterize the heterogeneity of murine plasmacytoid dendritic cells (pDCs) and to decipher their activation trajectory during a viral infection in vivo. To this end, individual splenic pDCs were transcriptionally profiled at ground state and at the time of their peak production of type I interferon (IFN-I) during mouse cytomegalovirus (MCMV) infection, with enrichment of IFN-I-producing pDCs based on the use of a reporter mouse strain.

2020-07-07 | GSE151246 | GEO

Single-cell analysis of mouse plasmacytoid dendritic cells (pDCs) unravels their activation trajectory and their molecular regulation in vivo during a viral infection [Ss2_pDC2]

Project description:The aim of the project is to characterize the heterogeneity of murine plasmacytoid dendritic cells (pDCs) and to decipher their activation trajectory during a viral infection in vivo. To this end, individual splenic pDCs were transcriptionally profiled at ground state and at the time of their peak production of type I interferon (IFN-I) during mouse cytomegalovirus infection, with enrichment of IFN-I-producing pDCs based on the use of a reporter mouse strain and on their down-regulation of LIFR.

2020-07-07 | GSE151247 | GEO

Transcription profiling of mouse Plasmacytoid dendritic cells (pDCs) from E2-2 heterozygotes

Project description:Analysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes. Experiment Overall Design: Duplicates of both wild type and heterozygous pDCs were used

2008-10-26 | E-GEOD-12505 | biostudies-arrayexpress

IFN? expression is restricted to a subpopulation of splenic pDCs exhibiting a specific immune modulatory transcriptome signature

Project description:Type I IFNs are critical in initiating protective antiviral immune responses and plasmacytoid DCs (pDCs) represent a major source of these cytokines. Here we show that only few pDCs are capable to produce IFN? after virus infection or CpG stimulation. Utilizing IFN?/YFP reporter mice, we identify these IFN?-producing cells in the spleen as a CCR9+CD9- pDC subset exclusively localized within the T/B cell zones. IFN?-producing pDCs exhibit a distinct transcriptome profile with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation. These distinctive characteristics of IFN?-producing pDCs are independent of the type I IFN receptor mediated feedback loop. Furthermore, IFN?-producing pDCs exhibit enhanced CCR7-dependent migratory properties in vitro and in a peritoneal inflammation model they effectively recruit T cells in vivo. We define “professional type I IFN-producing cells” as a distinct subset of pDCs specialized in coordinating cellular immune responses. IFN? associated gene expression in ex vivo sorted IFN?/YFPpos vs. IFN?/YFPneg splenic pDCs was measured at 6 hr after i.v. injection of CpG 1668 complexed to DOTAP. Two independent experiments were performed using pooled samples of at least 12 mice per experiment.

2015-05-27 | E-GEOD-68788 | biostudies-arrayexpress

Proteomic and single-cell transcriptomic dissection of human plasmacytoid dendritic cell response to influenza virus

Project description:Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons [IFN-I]. This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in response to challenge with live influenza H1N1. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversification following stimulation. Our data reveal an abundance of protein species released by pDCs in addition to IFN-I, and evidence highly specialized roles within the pDC population ranging from dedicated cytokine super-producers to cells with APC-like functions. Moreover, dynamic expression of transcription factors and surface markers characterize activated pDC fates.

2021-11-12 | MSV000088375 | MassIVE

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