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Direct regulation of T cell exhaustion by NFAT [ChIP-Seq]

GSE64407 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 12 samples Submitted 2015/02/13 Platform GPL14602
Summary
During persistent antigen stimulation, CD8+ cytolytic T cells (CTL) show a gradual decrease in effector function, or “exhaustion”, which impairs the immune response to tumors and infections. Here we show that NFAT, a transcription factor with an established role in T cell activation, in parallel controls a second transcriptional program conferring the characteristic features of CD8+ T cell exhaustion, including upregulation of genes encoding inhibitory cell surface receptors and diminished TCR signaling. Expression of an engineered NFAT1, which induces this negative regulatory program in the absence of the effector program, interferes with the ability of CD8+ T cells to protect against Listeria infection or attenuate tumor growth in vivo. NFAT elicits this second program of gene expression in large part by binding to a subset of the sites occupied by NFAT during a typical effector response, suggesting that a balance between the two pathways determines the outcome of TCR signaling.
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Direct links to NCBI, no account and no request form: the whole study as GSE64407_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA270948 and SRA study SRP051442. Searching any of these in the dataset finder brings you back here.

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