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RARa restrains CD8 T cell effector program [scRNA-seq]

ABSTRACT: RARa restrains CD8 T cell effector program [scRNA-seq]

PROVIDER: PRJNA1072642 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27846548_1.fastq.gz	Fastqsanger.gz
	SRR27846548_2.fastq.gz	Fastqsanger.gz
	SRR27846549_1.fastq.gz	Fastqsanger.gz
	SRR27846549_2.fastq.gz	Fastqsanger.gz
	SRR27846550_1.fastq.gz	Fastqsanger.gz

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Project description:The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved. P14 TCR transgenic CD8+ T cells from wild-type or BATF-/- mice were examined either as naÃ¯ve cells or after 3 days of in vitro stimulation with antibodies to CD3 and CD28 in the presence of IL-2

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