作者: Claudia Sorrentino , Fokhrul Hossain , Paulo C. Rodriguez , Rosa A. Sierra , Antonio Pannuti
关键词: Adenosine A2A receptor 、 Ionomycin 、 T-cell receptor 、 Cell biology 、 Granzyme B production 、 Notch 1 、 Signal transduction 、 Chemistry 、 Receptor 、 Agonist
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