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Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18608-13. doi: 10.1073/pnas.1317191110. Epub 2013 Oct 25.

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

Author information

1
Signaling and Gene Expression Division, La Jolla Institute for Allergy and Immunology, San Diego, CA 92037.

Erratum in

  • Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):2047.

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.

KEYWORDS:

CD8+ T-cell response; posttranscriptional regulation

PMID:
24163352
PMCID:
PMC3831973
DOI:
10.1073/pnas.1317191110
[Indexed for MEDLINE]
Free PMC Article

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