title: A role for Dicer in immune regulation.
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.
authors.affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Cobb
authors.forename: Arnulf
authors.initials: A
authors.lastname: Hertweck
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: Eric
authors.initials: E
authors.lastname: O'Connor
authors.forename: Daniel
authors.initials: D
authors.lastname: Graf
authors.forename: Terence
authors.initials: T
authors.lastname: Cook
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smale
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Livesey
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Fisher
authors.forename: Matthias
authors.initials: M
authors.lastname: Merkenschlager
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis; D043244:Ribonuclease III / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D043244:Ribonuclease III