A role for Dicer in immune regulation.
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.
Cobb
Bradley S
BS
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK.
Hertweck
Arnulf
A
Smith
James
J
O'Connor
Eric
E
Graf
Daniel
D
Cook
Terence
T
Smale
Stephen T
ST
Sakaguchi
Shimon
S
Livesey
Frederick J
FJ
Fisher
Amanda G
AG
Merkenschlager
Matthias
M
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
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D043244:Ribonuclease III