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A role for Dicer in immune regulation.

  • Author(s): 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
  • et al.
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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