Dicer-dependent microRNA pathway safeguards regulatory T cell function

Adrian Liston, Li Fan Lu, Donal O'Carroll, Alexander Tarakhovsky, Alexander Y. Rudensky

    Research output: Contribution to journalArticlepeer-review

    353 Citations (Scopus)

    Abstract

    Regulatory T (T reg) cells are indispensable for preventing autoimmunity. Incumbent to this role is the ability of T reg cells to exert their suppressor function under inflammatory conditions. We found that T reg cell-mediated tolerance is critically dependent on the Dicer-controlled microRNA (miRNA) pathway. Depletion of miRNA within the T reg cell lineage resulted in fatal autoimmunity indistinguishable from that in T reg cell-deficient mice. In disease-free mice lacking Dicer in all T cells or harboring both Dicer-deficient and -sufficient T reg cells, Dicer-deficient T reg cells were suppressive, albeit to a lesser degree, whereas their homeostatic potential was diminished as compared with their Dicer-sufficient counterparts. However, in diseased mice, Dicer-deficient T reg cells completely lost suppressor capacity. Thus, miRNA preserve the T reg cell functional program under inflammatory conditions.

    Original languageEnglish
    Pages (from-to)1993-2004
    Number of pages12
    JournalJournal of Experimental Medicine
    Volume205
    Issue number9
    DOIs
    Publication statusPublished - 1 Sept 2008

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