MicroRNA-directed program of cytotoxic CD8(+) T-cell differentiation

作者：Trifari Sara; Pipkin Matthew E; Bandukwala Hozefa S; Aijo Tarmo; Bassein Jed; Chen Runqiang; Martinez Gustavo J; Rao Anjana^*

来源：Proceedings of the National Academy of Sciences, 2013, 110(46): 18608-18613.

DOI：10.1073/pnas.1317191110

• CD8(+) T-cell response
• posttranscriptional regulation

Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTLs, and that deletion or depletion of Dicer in mouse or human activated CD8(+) T cells causes up-regulation of perforin, granzymes, and effector cytokines. Genome-wide analysis of microRNA (miR, miRNA) changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of an miRNA network that controls perforin, eomesodermin, and IL-2R alpha expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation, and antigenic stimulation. Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation.

• 出版日期2013-11-12