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GSE52081
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The physiological function of the immune system and the response to therapeutic immunomodulators may be sensitive to combinatorial cytokine micro-environments that shape the responses of specific immune cells. Previous work shows that paracrine cytokines released by virus-infected human dendritic cells (DC) can dictate the maturation state of nave DCs. To understand the effects of paracrine signaling, we systematically studied the effects of combinations cytokines in this complex mixture in generating an antiviral state. After nave DCs were exposed to either IFN or to paracrine signaling released by DCs infected by Newcastle Disease Virus (NDV), microarray analysis revealed a large number of genes that were differently regulated by the DC-secreted paracrine signaling. In order to identify the cytokine mechanisms involved, we identified 20 cytokines secreted by NDV infected DCs for which the corresponding receptor gene is expressed in nave DCs. By exposing cells to all combinations of 19 cytokines (leave-one-out studies) we identified 5 cytokines (IFN, TNF, IL-1, TNFSF15 and IL28) as candidates for regulating DC maturation markers. Subsequent experiments identified IFN, TNF and IL1 as the major synergistic contributors to this antiviral state. This finding was supported by infection studies in vitro, by T cell activation studies and by in vivo infection studies in mouse. Combination of cytokines can cause response states in DCs that differ from those achieved by the individual cytokines alone. These results suggest that the cytokine microenvironment may act via a combinatorial code to direct the response state of specific immune cells. Further elucidation of this code may provide insight into responses to infection and neoplasia as well as guide the development of combinatorial cytokine immunomodulation for infectious, autoimmune and immunosurveillance-related diseases.
Publication Title
Combinatorial cytokine code generates anti-viral state in dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray to characterize interferon stimulated genes in dendritic cells
Publication Title
Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 150 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 120 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 384 Downloadable Samples
NextSeq 500
Description
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact. Overall design: CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
Publication Title
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 383 Downloadable Samples
- NextSeq 500
Description
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact. Overall design: CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
Publication Title
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 384 Downloadable Samples
- NextSeq 500
Description
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact. Overall design: CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
Publication Title
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 383 Downloadable Samples
- NextSeq 500
Description
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact. Overall design: CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
Publication Title
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples