Title: MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation.

Authors: Trifari, Sara; Pipkin, Matthew E; Bandukwala, Hozefa S; Äijö, Tarmo; Bassein, Jed; Chen, Runqiang; Martinez, Gustavo J; Rao, Anjana

Published In Proc Natl Acad Sci U S A, (2013 Nov 12)

Abstract: 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-2Rα 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.

PubMed ID: 24163352

MeSH Terms: Adoptive Transfer; Animals; Blotting, Western; Cell Differentiation/physiology*; Computational Biology; DNA Primers/genetics; Gene Expression Regulation/immunology*; Granzymes/metabolism; Humans; Interleukin-2 Receptor alpha Subunit/metabolism; Mice; MicroRNAs/metabolism*; Perforin/metabolism; Real-Time Polymerase Chain Reaction; Ribonuclease III/metabolism*; Sequence Analysis, DNA; Signal Transduction/immunology*; T-Lymphocytes, Cytotoxic/physiology*; Virus Diseases/immunology*