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J Exp Med. 2008 Sep 1;205(9):1993-2004. doi: 10.1084/jem.20081062. Epub 2008 Aug 25.

Dicer-dependent microRNA pathway safeguards regulatory T cell function.

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1
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
18725526
PMCID:
PMC2526195
DOI:
10.1084/jem.20081062
[Indexed for MEDLINE]
Free PMC Article
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