First Author | Trifari S | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 46 | Pages | 18608-13 |
PubMed ID | 24163352 | Mgi Jnum | J:202902 |
Mgi Id | MGI:5523358 | Doi | 10.1073/pnas.1317191110 |
Citation | Trifari S, et al. (2013) MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation. Proc Natl Acad Sci U S A 110(46):18608-13 |
abstractText | 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-2Ralpha 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. |