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GSE44722
Homo sapiens
351 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 128 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
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.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 120 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
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.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 77 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
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.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell 'helper' population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 2 independent datasets; dataset1: total 9 samples (3 subjects, 3 groups, 3 replicates); dataset2: total 20 samples, 2 samples(PD1POS, Tfh) from each of 10 SLE patients
Publication Title
A CD4<sup>+</sup> T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- NextSeq 500
Description
A better understanding of the mechanisms involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR5- CXCR3+ PD1hi CD4+ T cell 'helper' population distinct from follicular helper T cells (Tfh) and expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFN??and high levels of IL10. Additionally, they accumulate high amounts of mitochondrial ROS (mtROS) as the result of reverse electron transport (RET) fueled by succinate. These cells provide potent help to B cells through the synergistic effect of IL10 and succinate. Cells with similar phenotype and function are generated in vitro upon priming naïve CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)-activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 9 total samples; 3 groups of 3 biological replicates: control group Th0, co-culture group CpGA-pDC, and co-culture group Ox mtDNA-pDC
Publication Title
A CD4<sup>+</sup> T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Development of T-cells provides a unique opportunity to study cell-fate determination due to the accessability and the well defined stages of development. In order to understand the genetic programs underlying fetal and adult Tcell fate specification we subjected highly purified fetal and adult T-cell progenitor populations to a genomewide transcriptional analysis. The aim was to identify molecular elements that govern T-cell fate specification as a whole but ultimately to isolate elements that were specific for a given population in a specific developmental window.
Publication Title
Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Visceral leishmaniasis (VL), caused by Leishmania spp protozoan parasites, can provoke overwhelming and protracted epidemics, with high casefatality rates. Despite extensive efforts towards the development of an effective prophylactic vaccine, no promising vaccine is available yet for humans. Multi-epitope peptide based vaccine development is manifesting as the new era of vaccination strategies against VL. Aim of the study was the design of chimeric peptides from immunogenic L. infantum proteins for encapsulation in PLGA nanoparticles (NPs) alone or in combination with MPLA adjuvant, or in PLGA NPs surface modified with an octapeptide mimicking TNF-alpha for DCs targeting, in order to construct a peptide-based nanovaccine. The in vitro evaluation of the above nanoformulations was performed in DCs isolated from HLA-A2.1 transgenic mice. Characterization of DCs transcriptional responses to these vaccine candidates via microarrays could improve our understanding of their mechanisms of action on DCs' functional differentiation and the type of adaptive immunity subsequently induced.
Publication Title
A Poly(Lactic-<i>co</i>-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different <i>Leishmania infantum</i> Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8<sup>+</sup> T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Visceral leishmaniasis (VL) caused by Leishmania donovani and L. infantum is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development. Thus, new strategies are needed to improve vaccine efficacy based on a better understanding of the mechanisms mediating protective immunity and mechanisms of host immune responses subversion by immunopathogenic components of Leishmania. In the present study, determination of the immune mechanisms related to infection or protective immune responses against VL using an experimental nanovaccine as a vaccine model was conducted through microarray analysis.
Publication Title
Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice.
Sample Metadata Fields
No sample metadata fields
View Samples