Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s

ABSTRACT: 8 ligand), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142630 | GEO | 2020/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s [Affy]

Project description:Stimulation of dendritic cells (DC) is considered critical in cancer immunotherapy. BATF-3–dependent subsets, that express in humans BDCA-3 (CD141), promote CD8 T-cell cross-priming against tumor antigens. Here, we evaluate two clinical grade stimuli for peripheral blood cDC1 myeloid dendritic cells (mDCs), a rare DC subset that is currently being explored for use in immunotherapy. In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. Specifically, we analyzed the mRNA of cDC1 mDCs from five human donors upon activation with two clinical-grade adjuvants, Hiltonol (poly IC, a TLR3 ligand, called Stimulus 1 in the description below) and protamine RNA (pRNA, aTLR7/8 ligand, Stimulus 2), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.

2023-09-30 | GSE239895 | GEO

Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s [RNA-seq]

Project description:Stimulation of dendritic cells (DC) is considered critical in cancer immunotherapy. BATF-3–dependent subsets, that express in humans BDCA-3 (CD141), promote CD8 T-cell cross-priming against tumor antigens. Here, we evaluate two clinical grade stimuli for peripheral blood cDC1 myeloid dendritic cells (mDCs), a rare DC subset that is currently being explored for use in immunotherapy. In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. Specifically, we analyzed the mRNA of cDC1 mDCs from five human donors upon activation with two clinical-grade adjuvants, Hiltonol (poly IC, a TLR3 ligand, called "Stimulus 1" in the description below) and protamine RNA (pRNA, aTLR7/8 ligand, "Stimulus 2"), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.

2023-09-30 | GSE239898 | GEO

Gene expression profile of CD141+DNGR-1+ dendritic cells (cDC1s) derived in vitro from multipotent lymphoid progenitors (MLP) or common myeloid progenitors (CMP)

Project description:CD141+DNGR-1+ cDC1 have a dual origin. Both MLP and CMP can differentiate in CD141+DNGR-1+ cDC1s. Using Affymetrix microarrays (GeneChip Human Gene 2.0 ST) we compared gene expression of CD141+DNGR-1+ cDC1s originating either from MLPs or CMPs

2017-07-18 | GSE98957 | GEO

Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

Project description:The IRF8-dependent subset of classical dendritic cells (cDC), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor Flt3 ligand (Flt3L) yields very few cDC1 (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) optimize Flt3L-driven development of cDC1 from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1 with the phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling ex vivo cDC1. OP9-DL1-induced cDC1 showed preferential migration towards Ccr7 ligands in vitro and superior T cell cross-priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1 from human bone marrow progenitors cultured with Flt3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1 for functional studies and therapeutic applications.

2018-06-05 | GSE110577 | GEO

Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-30 | GSE239899 | GEO

Adjuvant induced attenuation of excessive inflammation in mice infected with pandemic H1N1 (H1N1pdm) virus

Project description:The reassorted human 2009 pandemic H1N1 (H1N1pdm) virus infected millions of people and caused thousands of deaths with associated immunopathology. Traditional immunosuppressants have limited capabilities in controlling inflammatory responses associated with severe influenza infections. A new therapeutic strategy, therefore, must be developed. We evaluated several adjuvants including toll-like receptor (TLR) agonists, TLR independent adjuvants and Complete Freund’s adjuvant (CFA) for limiting severe H1N1pdm infection outcomes in a mouse model. In contrast to the TLR agonists and TLR independent adjuvants, CFA which contains multiple pattern recognition receptor (PRR) agonists significantly restrained pro-inflammatory responses and promoted survival in mice from lethal H1N1pdm infection. CFA reduced expression of the plamacytoid dendritic cell (pDC) markers and interferon alpha (IFN-α) after infection, whereas it elevated the T regulatory (Treg) cell suppressive molecules galectin-1 and CTLA-4 expression. Consequently, Th1 cell differentiation and CD8+ effector T cell responses were diminished via downregulated myeloid DC (mDC) costimulation. Furthermore, CTLA-4 expressing Treg cells were dramatically increased when the CFA primed splenocytes were restimulated with its stimuli-killed mycobacterium tuberculosis (M. TB). The elevated CTLA-4 on Treg cells led to reduced CD86 expressing pDCs/mDCs and less CD4+ effector T cells. Overall, our study highlights that the stimuli of innate immunity potentially controls overactive host immune responses in certain situations, and the uncovered mechanism(s) sheds light on the development of anti-influenza therapies. C57B6/J Mice were treated with CFA at day -2 and day 2 post H1N1pdm infection. Weight loss and lethality were monitored post infection. At day 3 and day 5 lung tissues were collected for RNA extraction and expression array analysis.

2014-09-10 | E-GEOD-41088 | biostudies-arrayexpress

Adjuvant induced attenuation of excessive inflammation in mice infected with pandemic H1N1 (H1N1pdm) virus

2014-09-10 | GSE41088 | GEO

Mass spectrometric characterization of HSV-1 L-particles from human dendritic cells and BHK21 cells and analysis of their functional role

Project description:Herpes simplex virus type 1 (HSV-1) is a very common human pathogenic virus among the world’s 12 population. The lytic replication cycle of HSV-1 is, amongst others, characterized by a tripartite viral 13 gene expression cascade, the assembly of nucleocapsids involving their subsequent nuclear egress, 14 tegumentation, re-envelopment and the final release of progeny viral particles. During productive 15 infection of a multitude of different cell types, HSV-1 generates not only infectious heavy (H-) 16 particles, but also non-infectious light (L-) particles, lacking the capsid. In monocyte-derived mature 17 dendritic cells (mDCs), HSV-1 causes a non-productive infection with the predominant release of L-18 particles. Until now, the generation and function of L-particles is not well understood, however, they 19 are described as factors transferring viral components to the cellular microenvironment. To obtain 20 deeper insights into the L-particle composition, we performed a mass-spectrometry-based analysis of 21 L-particles derived from HSV-1-infected mDCs or BHK21 cells and H-particles from the latter one. 22 In total, we detected 63 viral proteins in both H- and L-particle preparations derived from HSV-1-23 infected BHK21 cells. In L-particles from HSV-1-infected mDCs we identified 41 viral proteins 24 which are differentially distributed compared to L-particles from BHK21 cells. In this study, we 25 present data suggesting that L-particles modify mDCs and suppress their T cell stimulatory capacity. 26 Due to the plethora of specific viral proteins incorporated into and transmitted by L-particles, it is 27 tempting to speculate that L-particles manipulate non-infected bystander cells for the benefit of the 28 virus.

2021-09-09 | PXD020845 | Pride

Mass spectrometric characterization of HSV-1 L-particles from human dendritic cells and BHK21 cells and analysis of their functional role Part B

2021-09-09 | PXD020846 | Pride

RNA-seq of Zbtb10 Knockdown and Control cDC1 dendritic cells (Cd8+)

Project description:RNA-seq of the immune-suppressed cDC1 was done to look into the mechanism underlying TLR9. It was then compared with the inflammatory cDC1 DCs.

2021-09-03 | E-MTAB-9495 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data