Individual liver plasmacytoid dendritic cells are capable of producing IFNa and multiple additional cytokines during chronic HCV infection [exp1]
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PROVIDER: PRJNA553545 | ENA |
REPOSITORIES: ENA
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Project description:Individual liver plasmacytoid dendritic cells are capable of producing IFNa and multiple additional cytokines during chronic HCV infection
| PRJNA553540 | ENA
Project description:Plasmacytoid dendritic cells (pDCs) are ÒnaturalÓ interferon _ (IFN_)-producing cells. Despite their importance to antiviral defense, autoimmunity, and ischemic liver graft injury, because DC subsets are rare and heterogeneous, basic questions about liver pDC function and capacity to make cytokines remain unanswered. Previous investigations failed to consistently detect IFN_ mRNA in HCV-infected livers, suggesting that pDCs may be incapable of producing IFN_. We used a combination of molecular, biochemical, cytometric, and high-dimensional techniques to analyze DC frequencies/functions in liver and peripheral blood mononuclear cells (PBMCs) of hepatitis C virus (HCV)-infected patients, to examine correlations between DC function and gene expression of matched whole liver tissue and liver mononuclear cells (LMCs), and to determine if pDCs can produce multiple cytokines. T cells often produce multiple cytokines/chemokines but until recently technical limitations have precluded tests of polyfunctionality in individual pDCs. Mass cytometry (CyTOF) revealed that liver pDCs are the only LMC that produces detectable amounts of IFN_ in response TLR-7/8 stimulation. Liver pDCs secreted large quantities of IFN_ (~2 million molecules of IFN_/cell/hour) and produced more IFN_ than PBMCs after stimulation, p=0.0001. LMCs secreted >14-fold more IFN_ than IFN_ in 4 hours. Liver pDC frequency positively correlated with whole liver expression of ÒIFN_-responseÓ pathway (R2=0.58, p=0.007) and Òmonocyte surfaceÓ signature (R2=0.54, p=0.01). Mass cytometry revealed that IFN_-producing pDCs were highly polyfunctional; >90% also made 2-4 additional cytokines/chemokines of our test set of 10. Liver BDCA1 DCs, but not BDCA3 DCs, were similarly polyfunctional. pDCs from a healthy liver were also polyfunctional. Our data show that liver pDCs retain the ability to make abundant IFN_ during chronic HCV infection and produce many other immune modulators. Polyfunctional liver pDCs are likely to be key drivers of inflammation and immune activation during chronic HCV infection.
2019-07-10 | GSE134040 | GEO
Project description:Individual liver plasmacytoid dendritic cells are capable of producing IFNa and multiple additional cytokines during chronic HCV infection [exp2]
| PRJNA553544 | ENA
Project description:Plasmacytoid dendritic cells (pDCs) are ÒnaturalÓ interferon _ (IFN_)-producing cells. Despite their importance to antiviral defense, autoimmunity, and ischemic liver graft injury, because DC subsets are rare and heterogeneous, basic questions about liver pDC function and capacity to make cytokines remain unanswered. Previous investigations failed to consistently detect IFN_ mRNA in HCV-infected livers, suggesting that pDCs may be incapable of producing IFN_. We used a combination of molecular, biochemical, cytometric, and high-dimensional techniques to analyze DC frequencies/functions in liver and peripheral blood mononuclear cells (PBMCs) of hepatitis C virus (HCV)-infected patients, to examine correlations between DC function and gene expression of matched whole liver tissue and liver mononuclear cells (LMCs), and to determine if pDCs can produce multiple cytokines. T cells often produce multiple cytokines/chemokines but until recently technical limitations have precluded tests of polyfunctionality in individual pDCs. Mass cytometry (CyTOF) revealed that liver pDCs are the only LMC that produces detectable amounts of IFN_ in response TLR-7/8 stimulation. Liver pDCs secreted large quantities of IFN_ (~2 million molecules of IFN_/cell/hour) and produced more IFN_ than PBMCs after stimulation, p=0.0001. LMCs secreted >14-fold more IFN_ than IFN_ in 4 hours. Liver pDC frequency positively correlated with whole liver expression of ÒIFN_-responseÓ pathway (R2=0.58, p=0.007) and Òmonocyte surfaceÓ signature (R2=0.54, p=0.01). Mass cytometry revealed that IFN_-producing pDCs were highly polyfunctional; >90% also made 2-4 additional cytokines/chemokines of our test set of 10. Liver BDCA1 DCs, but not BDCA3 DCs, were similarly polyfunctional. pDCs from a healthy liver were also polyfunctional. Our data show that liver pDCs retain the ability to make abundant IFN_ during chronic HCV infection and produce many other immune modulators. Polyfunctional liver pDCs are likely to be key drivers of inflammation and immune activation during chronic HCV infection.
2019-07-10 | GSE134041 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-07-10 | GSE134042 | GEO
Project description:Plasmacytoid dendritic cells (pDCs) are "natural" interferon ? (IFN?)-producing cells. Despite their importance to antiviral defense, autoimmunity, and ischemic liver graft injury, because DC subsets are rare and heterogeneous, basic questions about liver pDC function and capacity to make cytokines remain unanswered. Previous investigations failed to consistently detect IFN? mRNA in HCV-infected livers, suggesting that pDCs may be incapable of producing IFN?. We used a combination of molecular, biochemical, cytometric, and high-dimensional techniques to analyze DC frequencies/functions in liver and peripheral blood mononuclear cells (PBMCs) of hepatitis C virus (HCV)-infected patients, to examine correlations between DC function and gene expression of matched whole liver tissue and liver mononuclear cells (LMCs), and to determine if pDCs can produce multiple cytokines. T cells often produce multiple cytokines/chemokines but until recently technical limitations have precluded tests of polyfunctionality in individual pDCs. Mass cytometry (CyTOF) revealed that liver pDCs are the only LMC that produces detectable amounts of IFN? in response TLR-7/8 stimulation. Liver pDCs secreted large quantities of IFN? (~2 million molecules of IFN?/cell/hour) and produced more IFN? than PBMCs after stimulation, p = 0.0001. LMCs secreted >14-fold more IFN? than IFN? in 4 hours. Liver pDC frequency positively correlated with whole liver expression of "IFN?-response" pathway (R2 = 0.58, p = 0.007) and "monocyte surface" signature (R2 = 0.54, p = 0.01). Mass cytometry revealed that IFN?-producing pDCs were highly polyfunctional; >90% also made 2-4 additional cytokines/chemokines of our test set of 10. Liver BDCA1 DCs, but not BDCA3 DCs, were similarly polyfunctional. pDCs from a healthy liver were also polyfunctional. Our data show that liver pDCs retain the ability to make abundant IFN? during chronic HCV infection and produce many other immune modulators. Polyfunctional liver pDCs are likely to be key drivers of inflammation and immune activation during chronic HCV infection.
| S-EPMC6687199 | biostudies-literature
Project description:B cells respond robustly to IFNa. Here we analyze gene expression profiles of primary murine splenic B cells treated with 10 fold serially diluted IFNa in vitro. We explore sensitivity to ISGs to IFNa as they relate to dose. Generally ISGs do not cluster significantly in a dose dependent manner. However there are notable spreads in sensitivity to IFNa.
2015-11-20 | GSE75194 | GEO
Project description:We report the grobal gene expression in follicular (FO) B cells stimulated with CpG, IFNa, and CpG plus IFNa for 12 hours prior to the onset of PC differentiation. We found that stimulation with CpG plus IFNa upregulates metabolic processes compared to stimulation with CpG alone. This study highlight the pivotal role of IFNa in determining the fate of PC differentiation of TLR9-activated FO B cells.
2024-04-22 | GSE244442 | GEO
Project description:B cells respond robustly to IFNa. Here we analyze gene expression profiles of primary murine splenic B cells treated with 10 fold serially diluted IFNa in vitro. We explore sensitivity to ISGs to IFNa as they relate to dose. Generally ISGs do not cluster significantly in a dose dependent manner. However there are notable spreads in sensitivity to IFNa. Splenic B cells were isolated by negative selection from 6wk old male C57BL/6 mice. These were cultured with IFNa (0U/ml-10 000U/ml) for 2hrs in vitro. Cells were then transferred directly into TriZol. RNA was prepared in Trizol for gene expression profiling by Affymetrix Mouse Gene 1.0 ST Arrays in triplicate for each concentration of IFNa.
2015-11-20 | E-GEOD-75194 | biostudies-arrayexpress
Project description:We report cell specific responses to IFNa in 11 different peripheral immunocyte populations in the mouse. These cells represent the core ImmGen immunocyte lineage panel. Profiles from these were used to analyze cell specific responses to IFNa. In general a core set of ISG transcripts are induced in all cells. Smaller sets of ISGs were induced in a cell specific manner. In particular, splenic granulocytes and dendritic cells show restriced indcution of sets of ISGs.
2015-11-20 | GSE75202 | GEO