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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*


  • DNA Primers
  • Interleukin-2 Receptor alpha Subunit
  • MIRN139 microRNA, mouse
  • MicroRNAs
  • Mirn150 microRNA, mouse
  • Perforin
  • Ribonuclease III
  • Granzymes