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

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

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    56 Citations (Scopus)

    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.

    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
    DOIs
    Publication statusPublished - 12 Nov 2013
    MoE publication typeA1 Journal article-refereed

    Keywords

    • CD8T-cell response
    • Posttranscriptional regulation

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