A role for Dicer in immune regulation

被引：455

作者：

Cobb, Bradley S.

Hertweck, Arnulf

Smith, James

O'Connor, Eric

Graf, Daniel

Cook, Terence

Smale, Stephen T.

Sakaguchi, Shimon

Livesey, Frederick J.

Fisher, Amanda G.

Merkenschlager, Matthias ^{[1
]}

机构：

[1] Imperial Coll London, MRC, Ctr Clin Sci, Lymphocyte Dev Grp, London W12 0NN, England

[2] Imperial Coll London, MRC, Ctr Clin Sci, Div Invest Sci, London W12 0NN, England

[3] Imperial Coll London, MRC, Ctr Clin Sci, Flow Cytometry Facil, London W12 0NN, England

[4] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England

[5] Wellcome Trust CRUK Gurdon Inst, Cambridge CB2 1QN, England

[6] Biomed Sci Res Ctr Al Fleming, Inst Immunol, Vari 16672, Greece

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[9] Kyoto Univ, Inst Frontier Med Sci, Dept Expt Pathol, Kyoto 6068501, Japan

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2006年 / 203卷 / 11期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1084/jem.20061692

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell-like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor beta. These results suggest that T reg cell development involves Dicer-generated RNAs.

引用

页码：2519 / 2527

页数：9

共 44 条

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