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Next Generation Sequencing analysis using splenic CD8 T cells isolated from Wild Type-OT-I (WT) and NIK -CD4Cre-OT-I (KO) mice

ABSTRACT: Next Generation Sequencing analysis using splenic CD8 T cells isolated from Wild Type-OT-I (WT) and NIK -CD4Cre-OT-I (KO) mice

PROVIDER: PRJNA650383 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12371371_1.fastq.gz	Fastqsanger.gz
	SRR12371371_2.fastq.gz	Fastqsanger.gz
	SRR12371372_1.fastq.gz	Fastqsanger.gz
	SRR12371372_2.fastq.gz	Fastqsanger.gz
	SRR12371373_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Next Generation Sequencing analysis using splenic CD8 T cells isolated from Wild Type-OT-I (WT) and NIK -CD4Cre-OT-I (KO) mice

Project description:Metabolic reprograming towards aerobic glycolysis is a pivotal mechanism that shapes immune responses. While deregulated T cell metabolism is associated with autoimmune diseases, metabolic deficiency contributes to T cell exhaustion in tumor microenvironment. Here we describe a posttranslational mechanism of glycolysis regulation mediated by the NF-kB-inducing kinase (NIK). NIK deficiency impairs glycolysis induction, rendering CD8 effector T cells hypofunctional with features of exhaustion in tumor microenvironment. Conversely, ectopic expression of NIK promotes CD8 T cell metabolism and prevents exhaustion, thereby profoundly enhancing antitumor immunity and improving the efficacy of T cell adoptive therapy. Interestingly, although NIK is known as a kinase mediating activation of noncanonical NF-kB, NIK regulates T cell metabolism via an NF-kB-independent mechanism that involves stabilization of hexokinase 2 (HK2), a rate-limiting enzyme of the glycolytic pathway. NIK deficiency causes autophagic degradation of HK2, at least in part due to aberrant ROS accumulation. NIK phosphorylates, and maintains the activity of, glucose-6-phosphate dehydrogenase (G6PD), an enzyme mediating production of the antioxidant NADPH required for preventing ROS accumulation and oxidative stress. We provide genetic evidence that the G6PD-NADPH redox system has a vital role in regulating HK2 stability and metabolism in activated T cells. These findings establish NIK as a pivotal regulator of T cell metabolism and highlight a posttranslational mechanism of metabolic regulation involving the G6PD-NADPH redox system.

2020-10-02 | GSE155576 | GEO

Next Generation Sequencing analysis using splenic cells freshly isolated from Wild Type-OT-I (WT) and OTUB1-CD4Cre-OT-I (KO) mice

Project description:Next Generation Sequencing analysis using splenic cells freshly isolated from Wild Type-OT-I (WT) and OTUB1-CD4Cre-OT-I (KO) mice

| PRJNA523247 | ENA

Next Generation Sequencing analysis using splenic cells freshly isolated from Wild Type-OT-I (WT) and OTUB1-CD4Cre-OT-I (KO) mice

Project description:CD8 T cells play a central role in immune responses against pathogens and cancer; however, CD8 T cells are typically rendered hypofunctional in tumor microenvironment due to tolerance to cancer cells and functional exhaustion. How to overcome CD8 T cell tolerance and stimulate strong antitumor responses has become an important issue for cancer immunotherapy 1,2. Here we identified the atypical deubiquitinase Otub1 as a pivotal regulator of CD8 T cell self-tolerance and antigen-stimulated responses. T cell-specific deletion of Otub1 in mice breaks CD8 T cell self-tolerance and promotes the metabolic reprograming and effector functions of activated CD8 T cells, resulting in profoundly stronger immunity against infections and tumorigenesis. The Otub1 deletion also synergizes with an immune checkpoint inhibitor in inducing tumor rejection and greatly increases the efficiency of an adoptive T cell transfer model of cancer immunotherapy. In line with these findings, the expression level of Otub1 is inversely associated with the abundance of CD8 effector T cell signature gene expression and patient survival in human melanoma. Mechanistically, Otub1 negatively regulates activation of AKT, a kinase that integrates the T cell receptor (TCR) and cytokine signals and mediates CD8 T cell metabolism and effector functions. Otub1 deficiency greatly promotes AKT activation by both the TCR signal and the immunostimulatory cytokine IL-15. Otub1 inhibits AKT ubiquitination and, thereby, suppresses its interaction with the membrane lipid phosphoinositol 3,4,5 triphosphate required for membrane translocation. These results demonstrate a ubiquitin-dependent mechanism that controls CD8 T cell responses and implicate Otub1 as a potential therapeutic target for cancer immunotherapy.

2019-05-16 | GSE126777 | GEO

Effect of NIK overexpression on Foxp3+CD4+ and Foxp3-CD4+ T cell subsets [Affymetrix]

Project description:We previously found that NF-kB inducing kinase (NIK) overexpression in T cells via CD4 promoter driven transgene induction caused lethal autoimmunity in mice. Autoimmunity was associated with increased conventional T cell effector function and decreased regulatory T cell (Foxp3+CD4+) suppression. The goal in this study was to elucidate global transcriptional changes in Foxp3+CD4+ and Foxp3-CD4+ T cells intrinsically caused by chronic NIK overexpression in these cell types. Total RNA from FACS-sorted NIKtg and WT Foxp3RFP+CD4+ and Foxp3RFP-CD4+ harvested from NIKtg/CD4Cre/Foxp3RFP + WT/Thy1.1/Foxp3RFP mixed bone marrow chimeric mice, >8 weeks after bone marrow reconstitution.

2016-04-29 | GSE80756 | GEO

NIK expression stimulated G6PD phosphorylation

Project description:Our findings establish NIK as a pivotal regulator of T cell metabolism in anti-tumor immunity and highlight a posttranslational mechanism of metabolic regulation involving the G6PD-NADPH redox system. CoIP assays revealed a strong physical interaction between NIK and G6PD in both T cells and transiently transfected 293 cells, suggesting G6PD to be a direct target of NIK. Using a phosphoprotein gel analysis approach, we demonstrated that NIK expression stimulated G6PD phosphorylation. To further study the mechanism, we performed mass spectrometry identify phosphorylation sites of G6PD stimulated by NIK

2020-10-05 | PXD020943 | Pride

RNA sequencing of naïve, Th1 and Th2 polarised live CD4+ T cells from CD4Cre+ and CD4Cre+DOT1LFL/FL mice

Project description:RNA sequencing of naïve, Th1 and Th2 polarised live CD4+ T cells from CD4Cre+ and CD4Cre+DOT1LFL/FL mice

2020-12-15 | GSE123966 | GEO

Comparasion between MCF7-NIK overexpressing cells, MCF7-control cells and MCF7-NIK depleted cells

Project description:Analysis of differentially expressed genes in MCF7 cancer cells transfected with an expression vector containing the ORF of NIK, a shRNA of NIK and a control shRNA. Transient transfections were performed in triplicates . We use micorarrays to elucidate the machanisms by which NIK regulates stem cells biology

2015-11-30 | GSE63382 | GEO

RNA-seq Analysis of Transcriptomes in β-Gal-overexpressing, NIK-overexpressing, and NIK(KA)-overexpressing αTC1-6 cells

Project description:Purpose: The goal of this study is to determine the molecular mechanisms involved in the NIK regulation of α cell function. Methods: mRNA profiles of β-Gal control, NIK, and NIK(KA) overexpressed αTC1-6 cells were generated by deep sequencing using an Illumina Hiseq platform. Paired-end clean reads were aligned to the mouse reference genome(Ensemble_GRCm38.89) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of NIK-overexpressing aTC1-6 cell transcriptomes, generated by RNA-seq technology. Our results show that 328 genes were upregulated and 48 genes were downregulated following NIK overexpression. GO analysis indicated that the upregulated genes were primarily related to the immune response. KEGG pathway enrichment analysis showed that immune signaling pathways, including the TNF, NF-κB, and chemokine signaling pathways, were significantly activated by NIK overexpression in aTC1-6 cells, while genes related to metabolism-associated signal pathways were significantly decreased. NIK(KA), the dominant-negative mutant of NIK, does not affect gene expression in aTC1-6 cells.

2018-12-30 | GSE112511 | GEO

NIK/NF-kappaB2 regulated gene products.

Project description:This study aims at identifying genes that are NIK/NF-kappaB2 responsive in murine dendritic cells matured in vivo. Keywords: NIK/NF-kappaB2 responsive genes in dendritic cells after TLR/CD40 signaling

2008-03-05 | GSE7219 | GEO

RNA-seq analysis of mRNA profiles in β-Gal-overexpressing, NIK-overexpressing, and NIK(KA)-overexpressing INS-1 832/13 cells

Project description:Purpose: The goal of this study is to investigate how NIK regulates islet β-cell function. Methods: mRNA profiles of β-Gal-overexpressing, NIK-overexpressing, and NIK(KA)-overexpressing INS-1 832/13 cells were generated by deep sequencing using an Illumina Hiseq platform. Paired-end clean reads were aligned to the rat reference genome (ftp://ftp.ensembl.org/pub/release-90/fasta/rattus_norvegicus/dna/) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of mRNA profiles in NIK-overexpressing and NIK(KA)-overexpressing INS-1 832/13 cells, generated by RNA-seq technology. Our results show that 471 genes were upregulated and 249 genes were downregulated following NIK overexpression. GO analysis indicated that the upregulated genes were primarily related to the immune response. KEGG pathway enrichment analysis showed that immune signaling pathways, including the TNF, NF-κB, antigen processing and presentation signaling pathways, were significantly activated by NIK overexpression in INS-1 832/13 cells, whereas genes related to insulin secretion and regulation of secretion were significantly decreased. NIK(KA), the dominant-negative mutant of NIK, does not induce the expression of genes related to immune response in INS-1 832/13 cells.

2020-07-28 | GSE130121 | GEO

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