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

Research output: Contribution to journalArticleScientificpeer-review

Researchers

  • Sara Trifari
  • Matthew E. Pipkin
  • Hozefa S. Bandukwala
  • Tarmo Äijö
  • Jed A. Bassein
  • Runqiang Chen
  • Gustavo J. Martinez
  • Anjana Rao

Research units

  • La Jolla Institute for Allergy and Immunology

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, in flammation, 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.

Details

Original languageEnglish
Pages (from-to)18608-18613
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number46
Publication statusPublished - 12 Nov 2013
MoE publication typeA1 Journal article-refereed

    Research areas

  • CD8T-cell response, Posttranscriptional regulation

ID: 12750268