The non-coding RNA miR-17~92 is a central mediator of T cell activation

摘要: T cell activation is paramount for productive adaptive immune responses. CD28 a key clinically targeted immunoregulatory receptor because it provides the prototypical costimulatory signal required activation. Therefore, precise understanding of molecular consequences costimulation has direct therapeutic relevance. Here, we uncover that microRNA cluster miR-17∼92 part program triggered by and hence Combining genetics, transcriptomics, bioinformatics biochemical miRNA:mRNA interaction maps demonstrate transgenic can cell-intrinsically largely overcome defects caused CD28-deficiency. promotes transcription proinflammatory gene signature enhancing calcineurin/NFAT pathway. binds to represses network genes including several negative regulators Finally, CD28-deficient cells exhibit derepressed target during activation, demonstrating this non-coding RNA shape transcriptome. Thus, propose constitutes central mediator integrating signals TCR costimulation. In model facilitates dampening breaks prevent