MiR-1224 Contributes To Ischemic Stroke-mediated Nature Killer Cell Dysfunction By Targeting Sp-1 Signaling Pathway

Brain ischemia compromises NK cell-mediated immune defenses via targeting neurogenic and intracellular pathways.While less is known about the posttranscriptional mechanisms that regulate NK cell function after ischemic stroke.In this study,adopting nanostring n Counter(?) miRNA array panel,we explored the Micro RNAs(miRNAs)profile of splenic NK cells in mice subjected to middle cerebral artery.We observed 10 miRNAs up-regulated in response to ischemia reperfusion.Among those miRNAs,miR-1224 profoundly increased 3 days after ischemia stroke.Transfection of miR-1224 mimics in NK cells resulted in a suppression of NK cell activity,while miR-1224 inhibitor resulted in NK cell activation and cytotoxicity,especially in periphery.Passive transfer of NK cells transfected with miR-1224 inhibitor prevented bacteria burden of lung after ischemia stroke,suggesting an enhanced immune defense of NK cells.Transcription factor Sp1,which controls cytokine/chemokine release of NK cells at transcription level,is a predicted target of miR-1224.The inhibition of miR-1224 on NK cell phenotype was blocked in Sp1 knockout mice.Together,these findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in Sp1-dependent manner after ischemic stroke.