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- W67324056 abstract "Abstract SLAM family receptors play a critical role in immune regulation. Their function is controlled primarily by SAP, EAT-2, and ERT adaptors. We have previously described a novel immunostimulatory function for EAT-2 in a vaccine model system. In the current work we sought to examine the mechanism of action of EAT-2 in APCs. Our results demonstrated that Ad vector infection itself of macrophages significantly (p<0.001) induced the transcription of the SLAM family member CRACC, but not other SLAM family members. In dramatic contrast, infection of macrophages with Ad-EAT2 significantly prevented Ad induced CRACC expression (p<0.001). FACS analysis confirmed that Ad mediated expression of EAT-2 also resulted in decreased protein levels of CRACC on APCs. By utilization of a variety of inhibitors, we confirmed that EAT-2 mediated suppression of CRACC required a functional ERK, but not Src-kinase, PI3K, or p38 pathways. In addition, blockade of ERK signaling abolished the ability of Ad-EAT2 to induce other innate immune response genes in APCs. Finally, utilization of immunoblot confirmed that Ad-EAT-2 significantly induced ERK activation in macrophages. Thus, EAT-2 over-expression by Adenovirus activates ERK pathway that inhibits Ad mediated induction of CRACC in APCs, an activity that correlates with increased induction of several innate immune response genes, as well the improved induction of antigen specific adaptive immune responses after Ad mediated transfer of immunogenic antigens." @default.
- W67324056 created "2016-06-24" @default.
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- W67324056 date "2011-04-01" @default.
- W67324056 modified "2023-10-16" @default.
- W67324056 title "Overexpression of EAT-2, a SLAM family receptor adaptor molecule, suppresses CRACC receptor expression on Antigen Presenting Cells in an ERK MAP kinase dependent mechanism (110.26)" @default.
- W67324056 doi "https://doi.org/10.4049/jimmunol.186.supp.110.26" @default.
- W67324056 hasPublicationYear "2011" @default.
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