A role for Dicer in immune regulation

Bradley S. Cobb(Imperial College London), Arnulf Hertweck, James Smith(The Gurdon Institute), Eric O’Connor(Imperial College London), Daniel Graf(Alexander Fleming Biomedical Sciences Research Center), Terence Cook, Stephen T. Smale(University of California, Los Angeles), Shimon Sakaguchi(Kyoto University), Frederick J. Livesey(University of Cambridge), Amanda G. Fisher, Matthias Merkenschlager
The Journal of Experimental Medicine
October 23, 2006
Cited by 522Open Access
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Abstract

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.


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