Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells.

作者: Claudia Sorrentino , Fokhrul Hossain , Paulo C. Rodriguez , Rosa A. Sierra , Antonio Pannuti

DOI: 10.3389/FIMMU.2019.00162

关键词: Adenosine A2A receptorIonomycinT-cell receptorCell biologyGranzyme B productionNotch 1Signal transductionChemistryReceptorAgonist

摘要: Notch receptors signaling is required for optimal T-cell activation and function. receptor (TCR) engagement can activate in T-cells a ligand-independent fashion. In this study, we examined the role of adenosine A2A (A2AR) pathway regulating activity Notch1 induced by TCR stimulation CD8+T-cells. A selective A2AR agonist decreased protein expression cleavage, reduced transcripts Notch1-target genes HES1 Myc activated Inhibition TCR-induced an was accompanied increased cAMP concentration mimicked forskolin. This effect associated with IFN- granzyme B production. The abrogated antagonist absent CD8+T-cells harvested from A2AR-/- mice. Stimulation levels inhibiting upstream signals, including ZAP70 phosphorylation, turn impairing generation active intracellular domain (N1ICD). Direct PKC PMA ionomycin bypassed A2AR-induced inhibition. Overexpression N1ICD prevented suppressive effects on proliferation cytokine release during activation. Our results identify as important regulator CD8+T-cells, target immune A2AR. We propose mechanism whereby impairs CD8 function through inhibition

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