The Journal of Experimental Medicine
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Published online 23 October 2006 doi:10.1084/jem.20061692
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 11, 2519-2527
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ARTICLE

 A role for Dicer in immune regulation

Bradley S. Cobb1, Arnulf Hertweck1, James Smith4, Eric O'Connor3, Daniel Graf6, Terence Cook2, Stephen T. Smale7, Shimon Sakaguchi8, Frederick J. Livesey4,5, Amanda G. Fisher1, and Matthias Merkenschlager1

1 Lymphocyte Development Group, 2 Division of Investigative Sciences, and 3 Flow Cytometry Facility, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK
4 Wellcome Trust/CRUK Gurdon Institute and 5 Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, England, UK
6 Institute of Immunology, Biomedical Sciences Research Center "Al. Fleming," 166 72 Vari, Greece
7 Department of Microbiology, Immunology, and Molecular Genetics, and Molecular Biology Institute, University of California, Los Angeles, CA 90095
8 Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8501, Japan

CORRESPONDENCE Matthias Merkenschlager: matthias.merkenschlager{at}csc.mrc.ac.uk

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 ß. These results suggest that T reg cell development involves Dicer-generated RNAs.

Abbreviations used: DN, double-negative; DP, double-positive; GITR, glucocorticoid-induced tumor necrosis factor receptor; miRNA, micro RNA; SAM, significance analysis of microarrays; SP, single-positive; T reg, regulatory T; UTR, untranslated region.

B.S. Cobb, A. Hertweck, and J. Smith contributed equally to this work.


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