Gene expression changes in anti-FcgRIIb treated DCs and monocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE7509 | GEO | 2007/04/30
SECONDARY ACCESSION(S): PRJNA100469
REPOSITORIES: GEO
Similar Datasets
Project description:The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies we have shown that selective antibody-mediated blockade of inhibitory FcgRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. Here we show that Fcg receptor (FcgR) mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation associated chemokines as well as type 1 interferon (IFN) response genes including the activation of signal transducer and activator of transcription 1 (STAT1). Experiment Overall Design: To further characterize FcgR mediated enhancement of DC function, we analyzed the gene expression profiles (GEP) of pure populations of monocyte-derived DCs from healthy donors (n=5) using Affymetrix Human Genome U133 Plus2.0 microarrays. Immature DCs cultured in 1% plasma were treated for 24 hours with either anti-FcgRIIB or isotype control antibody. To test whether FcgR mediated DC maturation was distinct from other maturation stimuli, we also compared DCs matured using the inflammatory cytokine cocktail (TNF-a, IL-1b, IL-6 and PGE2) commonly utilized in DC immunotherapy trials. In addition, we also treated Cd14+ monocytes (n=3) with anti-FcgRIIB antibody or isotype control. In order to better characterize the interferon responsive genes in DCs, we treated immature DCs (n=3) with 1000 U/ml of IFN-a2b.
2008-06-15 | E-GEOD-7509 | biostudies-arrayexpress
Project description:Conventional dendritic cells (cDCs) arise from committed precursor dendritic cells (pre DCs) in the bone marrow that continuously seed the periphery. Pre-DCs and other upstream progenitors proliferate and mature in response to Fms-related receptor tyrosine kinase 3 ligand (FLT3L), which is considered the most important cytokine for cDC development. However, other cytokines such as stem cell factor (SCF) and colony stimulating factor 1 (CSF1) were also shown to induce pre-DC maturation into DC-like cells. It is not completely understood which cells contribute to cDC development once pre-DCs arrive in peripheral tissues. Here, we analyzed the impact of lymph node (LN) fibroblastic stromal cells (FSCs) on the maturation of pre-DCs into cDCs. We could demonstrate that ex vivo isolated LN FSCs co-cultured with pre-DCs induce precursor maturation into DC-like cells, which were capable of efficiently promoting the proliferation of naïve CD4+ T cells. Interestingly, FSCs isolated from mesenteric lymph nodes (mLNs) or peripheral LNs (pLNs) induced DC-like cells with highly comparable transcriptomes, showing similarity to both ex vivo isolated DCs and macrophages based on characteristic signature genes. Finally, by performing supplementation and receptor blocking studies we could demonstrate that CSF1 is a driving factor for LN FSC-mediated pre-DC maturation into DC-like cells. In summary, we could identify CSF1 as a novel stromal cell-derived factor that supports the maturation of pre-DCs into cDCs within secondary lymphoid organs.
2024-09-01 | GSE184661 | GEO
Project description:Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population. We analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from unmanipulated mice. In addition, we analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from mixed BM chimeras (WT + IFNgR2KO) day 8 T. gondii infected.
2015-01-01 | E-GEOD-64594 | biostudies-arrayexpress
Project description:Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.
2015-01-01 | GSE64594 | GEO
Project description:microRNAs are crucial post-transcriptional regulators which contribute to the effect of sulforaphane in cancer and are also involved in the modulation of of many aspects of DC biology, including development, maturation, surface molecule expression and released cytokines We used microarrays to detail the regulation of miRNAs in human DCs by sulforaphane, underlying the regulation of different crucial DCs regulatory molecules and signaling pathways
2023-07-24 | GSE155246 | GEO
Project description:Regulation of RNA levels is critical for the response to external stimuli and determined through the interplay between RNA production, processing and degradation. Despite the centrality of these processes, most global studies of RNA regulation do not distinguish their separate contributions and relatively little is known about how they are temporally integrated. Here, we combine metabolic labeling of RNA with advanced RNA quantification assays and computational modeling to estimate RNA transcription and degradation during the response of immune dendritic cells (DCs) to pathogens, a critical and tightly regulated step in innate immunity. We find that transcription regulation plays a major role in shaping most temporal changes in RNA levels, but that changes in degradation rate are important for shaping sharp M-bM-^@M-^XpeakedM-bM-^@M-^Y responses. We find that transcription changes precede corresponding RNA changes by a small lag (15-30 min), which is shorter for induced than for repressed genes. Massively parallel sequencing of the entire RNA population M-bM-^@M-^S including non-polyadenylated transcripts M-bM-^@M-^S allows us to estimate RNA processing, and identify specific groups of transcripts, mostly cytokines and transcription factors, undergoing enhanced mRNA maturation. This suggests an additional role for splicing in regulating mRNA maturation. Our method provides a new quantitative approach to study key steps in the integrative process of RNA regulation. Sequencing of 4sU-labeled RNA taken from a 7 samples time-series (one sample every 1 hour) during the response of DCs to LPS stimulation. 4-thiouridine was added 45 minutes prior to sample collection. Data presented here for six timepoints: 0, 1, 3-6 hrs. 2hr timepoint not included.
2011-04-24 | E-GEOD-25432 | biostudies-arrayexpress
Project description:Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including complete variable regions in Ig light and heavy chains. Ig-MS uses new advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and degree of clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without DNA/RNA sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.
2021-05-27 | MSV000087529 | MassIVE
Project description:Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major ”inflammatory” dermal DC population in psoriasis vulgaris and CD1c+ DCs as the “resident” cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis.
2010-05-24 | GSE20264 | GEO
Project description:While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines. 38 samples of IFNa DC and 39 samples of IL4 DC stimulated by CL097, CpG 2006, CpG 2216, Flagellin, IFNa, IL10, IL15, IL1b, LPS, MDP, PAM3, Poly I:C, Poly I:C-LMW-Lyovec, R837 or TNFa
2014-10-22 | E-GEOD-44719 | biostudies-arrayexpress
Project description:While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines. 60 samples of IFNa DC and 60 samples of IL4 DC grown in Media and exposed to either H1N1 Brisbane virus, heat killed Staphylococcus aureus (HKSA), heat killed Salmonella enterica (HKSE), or nothing (media control) for 1h, 2h, 6h, 12h, or 24h
2014-10-22 | E-GEOD-44720 | biostudies-arrayexpress