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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [Kinetics RNA-seq]

ABSTRACT: Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [Kinetics RNA-seq]

PROVIDER: PRJNA801420 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17782900_1.fastq.gz	Fastqsanger.gz
	SRR17782900_2.fastq.gz	Fastqsanger.gz
	SRR17782901_1.fastq.gz	Fastqsanger.gz
	SRR17782901_2.fastq.gz	Fastqsanger.gz
	SRR17782902_1.fastq.gz	Fastqsanger.gz

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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [Kinetics RNA-seq]

Project description:While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response in vitro closely mirrored T cell features with IFN-I linked acute SARS-CoV-2 infection in human, with high LAG3 and decreased TIGIT expression. Finally, our gene regulatory network identified SP140 as a key regulator for differential LAG3 and TIGIT expression, which were validated at the level of protein expression. The construction of IFN-I regulatory networks with identification of unique transcription factors controlling co-inhibitory receptor expression may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity.

2022-01-31 | GSE195541 | GEO

Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells

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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [ATAC-seq]

Project description:Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [ATAC-seq]

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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [shRNA RNA-seq]

Project description:Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [shRNA RNA-seq]

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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells [ATAC-seq]

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KAP1 regulates elongation kinetics to activate signal-induced transcription

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Long noncoding RNA INCA1 regulates tumor interferon signaling

Project description:Tumor interferon signaling regulates the expression of immunosuppressive molecules and promotes cancer immune evasion. Although the role of long noncoding RNAs (lncRNAs) in the regulation of gene expression is now emerging, their function in tumor interferon signaling remains unexplored. We have identified the interferon-γ (IFNγ)-stimulated non-coding RNA 1 (INCA1) as a novel lncRNA expressed form the PD-L1 locus. INCA1 is expressed in multiple tumor types and its levels increase after IFNγ stimulation. In this study we performed transcriptome analysis (RNA-seq) of INCA1 knockdown cells and show that INCA1 regulates the expression of several interferon-stimulated genes. Overall, our findings reveal INCA1 as a critical component of the tumor interferon signaling.

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Global Interferon-stimulated Genes Interactome Network

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2019-03-01 | PXD012274 | Pride

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