ISCOM vaccines induce a balanced Th1/Th2 response and cytotoxic T lymphocytes. The adjuvant component, ISCOM-Matrix, consists of purified saponin fractions, cholesterol and phospholipids. The mode of action for the ISCOM-Matrix is known to some extent but still we lack knowledge of important segments in initiation of the immune response. The study was performed to analyze the early transcriptional responses to the ISCOM-Matrix alone, without the use of co-administered antigen. Matrix M (AbISCO 100) was given as intramuscular injection and after 24 hours the pigs was sacrificed for gene expression analysis, performed for the injection site and the draining lymph node.
Global transcriptional response to ISCOM-Matrix adjuvant at the site of administration and in the draining lymph node early after intramuscular injection in pigs.
Sex, Age, Specimen part, Treatment
View SamplesEts homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor, though its targets in lung epithelial cells are largely uncharacterized. RNA-seq after EHF depletion or overexpression showed significant alterations in the expression of genes involved in response to wounding. EHF knockdown also targeted genes in pathways of epithelial development and differentiation and locomotory behavior. Overall design: mRNA profiles from Calu-3 cells treated with negative control (NC) or EHF siRNA, in quintuplicate. mRNA profiles from 3 pcDNA (empty vector control) clones and 3 pcDNA-EHF overexpression A549 clones, 3-4 replicates each.
Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells.
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View SamplesFunctional characterization of human dendritic cell subsets is limited due to the very low frequency of these cells in vivo. We developed an in vitro culture system for the simultaneous generation of XCR1+ DCs and MoDCs from cord blood CD34+ cells. Their global gene expression profiles at steady state and under activation, phenotypes, morphologies and responses to different TLR ligands where characterized and compared with those of their in vivo counterparts. The study demonstrated that the XCR1+ DCs generated in vitro from cord blood CD34+ cells are equivalent to blood XCR1+ DCs and also allowed a rigorous comparison of this DC subset with MoDC which are often considered as the reference model for DCs. Altogether, our results showed that in vitro generated XCR1+ DCs are a better model for the study of blood DC than the conventionally used MoDCs.
Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesThis series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. These events occur independtly of type I interferons and of the microlofora, since the same maturation pattern is observed in XCR1+ tDcs from control, Ifnar1-KO and germ-free mice. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesXCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of nave CD8 T cells. This property was reported to be associated to the subset of the XCR1+ DC expressing IL-12b upon ex vivo stimulation for 24 h with a mixture of CpG, IFN-, and GM-CSF (Lin ML et al. Proc Natl Acad Sci USA. 2008. PMID: 18272486). DC found in the steady-state non-lymphoid tissues undergo an homeostatic, tolerogenic, maturation and migrate to the draining lymph nodes to interact with naive autoreactive T cells and induction their peripheral tolerance. In contrast, spleen DC are thought to exist solely in an immature state. The aim of this study was to re-examine heterogeneity within steady state spleen XCR1+ DC, in particular examining whether this population encompass a fraction of mature DCs as assessed through their expression of CCR7 and/or the Il12b gene. Indeed, we show that a small fraction of XCR1+ spleen DC constitutively mature into two distinct but likely successive activation stages characterized as CCR7+ and CCR7+Il12b+ respectively, and correlated with increasing ability to cross-present antigen to nave CD8 T cells. Transcriptomic analysis of the subsets of XCR1+ DC found in steady state spleen unexpectedly showed that their homeostatic maturation was unexpectedly associated with up-regulated of many genes thought to drive pro-inflammatory T-cell responses and previously found to be commonly induced upon maturation of distinct DC subsets in response to stimulation by various microbial-type stimuli (Vu Manh TP et al. Eur J Immunol. 2013. PMID: 23553052). Thus, our results reveal that spleen XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating upon homeostatic, tolerogenic, DC maturation versus microbial-type stimuli-induced, immunogenic, DC maturation.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
View SamplesThe goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of spleen XCR1+ DC early after MCMV infection in vivo, using on Affymetrix Mouse Gene 1.0 ST Array.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesThe goal of this experiment was to use global gene expression profiling to compare the global genetic reprogramming of spleen XCR1+ DC upon in vivo stimulation with a viral-type ligand, polyI:C which strongly induces type I interferons, versus with a ligand derived from an intracellular parasite which strongly induces IFN-g.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
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