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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [CRISPR screen]

ABSTRACT: CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [CRISPR screen]

PROVIDER: PRJNA821534 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18547514.fastq.gz	Fastqsanger.gz
	SRR18547515.fastq.gz	Fastqsanger.gz
	SRR18547516.fastq.gz	Fastqsanger.gz
	SRR18547517.fastq.gz	Fastqsanger.gz
	SRR18547518.fastq.gz	Fastqsanger.gz

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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity

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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [steady state]

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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [sgCcdc101 ATAC-seq]

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CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity.

Project description:Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2-4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein-protein interaction networks to identify regulatory modules that mediate immune receptor- and nutrient-dependent signalling to mTORC1 in mouse regulatory T (Treg) cells. SEC31A is identified to promote mTORC1 activation by interacting with the GATOR2 component SEC13 to protect it from SKP1-dependent proteasomal degradation. Accordingly, loss of SEC31A impairs T cell priming and Treg suppressive function in mice. In addition, the SWI/SNF complex restricts expression of the amino acid sensor CASTOR1, thereby enhancing mTORC1 activation. Moreover, we reveal that the CCDC101-associated SAGA complex is a potent inhibitor of mTORC1, which limits the expression of glucose and amino acid transporters and maintains T cell quiescence in vivo. Specific deletion of Ccdc101 in mouse Treg cells results in uncontrolled inflammation but improved antitumour immunity. Collectively, our results establish epigenetic and post-translational mechanisms that underpin how nutrient transporters, sensors and transducers interplay with immune signals for three-tiered regulation of mTORC1 activity and identify their pivotal roles in licensing T cell immunity and immune tolerance.

| S-EPMC8887674 | biostudies-literature

CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity

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

2021-09-26 | GSE160598 | GEO

CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [CRISPR screen]

Project description:Integrative system approaches uncover a three-tier system for the regulatory modules of nutrient signaling-dependent mTORC1 activation in primary T cells

2022-03-31 | GSE199813 | GEO

CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity [scRNA-seq]

Project description:Integrative system approaches uncover a three-tier system for the regulatory modules of nutrient signaling-dependent mTORC1 activation in regulatory T cells

2021-09-26 | GSE181341 | GEO

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