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• W1566018542 endingPage "4839" @default.
• W1566018542 startingPage "4832" @default.
• W1566018542 abstract "Abstract PD-1 is a transmembrane protein involved in the regulation of immunological tolerance. Multiple studies have reported an association between high levels of PD-1 expressed on T cell surfaces and exhaustion in lymphocyte populations when challenged by chronic viral infections, such as HIV. By using model systems consisting of murine EL4 cells, which constitutively express PD-1, and primary murine CD8 T cells that express PD-1 upon T cell stimulation, we have identified two tissue-specific hypersensitive sites at the 5′ CR of the PD-1 locus. Gene reporter assays in CD8 T cells have shown that one of these sites has robust transcriptional activity in response to cell stimulation. Cell treatment with the calcineurin inhibitor cyclosporine A or a NFAT-specific inhibitor led to a sharp reduction in PD-1 expression in the constitutive and inducible systems. Furthermore, analysis of this region by chromatin immunoprecipitation assay revealed NFATc1 binding associated with gene activation in EL4 and primary CD8 T cells. Mutation of the NFATc1 binding site in PD-1 reporter constructs resulted in a complete loss of promoter activity. Together, these results demonstrate that PD-1 gene regulation occurs in part via the recruitment of NFATc1 to a novel regulatory element at the pdcd1 locus and provides the molecular mechanism responsible for the induction of PD-1 in response to T cell stimulation." @default.
• W1566018542 created "2016-06-24" @default.
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• W1566018542 date "2008-10-01" @default.
• W1566018542 modified "2023-10-11" @default.
• W1566018542 title "NFATc1 Regulates PD-1 Expression upon T Cell Activation" @default.
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• W1566018542 doi "https://doi.org/10.4049/jimmunol.181.7.4832" @default.
• W1566018542 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2645436" @default.
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