Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A role for Dicer in immune regulation

ABSTRACT: A study of the miRNA profile CD4 T cells compared to T reg cells; of activated and naive T cells; and the miRNA profile conferred by enforced expression of Foxp3. Keywords: cell type comparison Fifteen arrays broken down into three broader experiments as referenced by series GSE6003 - a comparison of miRNA profile of natural T reg cells with conventional CD4+CD25- T cells; GSE6006 - a comparison of miRNA profile of activated T cells to naive T cells; and GSE6007 - comparison of miRNA profile of Foxp3-transduced activated T cells with control vector-transduced activated T cells.

ORGANISM(S): Mus musculus

SUBMITTER: Bradley Cobb

PROVIDER: E-GEOD-6056 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A role for Dicer in immune regulation.

Cobb Bradley S BS 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

The Journal of experimental medicine 20061023 11

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 ...[more]

PMID: 17060477

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Project description:Naturally occurring CD25+CD4+ regulatory T cells (T reg cells) are currently intensively characterized because of their major importance in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy. Originally, CD4+ T reg cells were identified exclusively by the constitutive expression of CD25, and many in vivo experiments have been performed using depleting antibodies directed against CD25. However, both the existence of CD25– T reg cells, especially within peripheral tissues, as well as the expression of CD25 on activated conventional T cells, which precludes discrimination between T reg cells and activated conventional T cells, limits the interpretation of data obtained by the use of anti-CD25 depleting antibodies. The most specific T reg cell marker currently known is the forkhead box transcription factor Foxp3, which has been shown to be expressed specifically in mouse CD4+ T reg cells and acts as a master switch in the regulation of their development and function. To address the question of the in vivo role of T reg cells in immunopathology, we have generated bacterial artificial chromosome (BAC)–transgenic mice termed depletion of regulatory T cell (DEREG) mice, which express a diphtheria toxin receptor (DTR) enhanced GFP (eGFP) fusion protein under the control of the foxp3 locus, allowing both detection and inducible depletion of Foxp3+ T reg cells. The gene expression profile of both CD4+eGFP+FoxP3+ and CD4+eGFPnegFoxP3neg cells isolated from DEREG mice was here analyzed by micro array. Keywords: DEREG, FoxP3, FoxP3-EGFP, mouse, regulatory T cell, CD4 CD4+GFP+FoxP3+ and CD4+GFPnegFoxP3neg cells were isolated from DEREG mice by negative selection of CD4+ T cells (Invitrogen Kit) and subsequent FACS sorting for GFP+ and GFPneg cells. Purity was greater than 99 %. cRNA was prepared according to the Affymetrix Labeling Protocol, fragmented and hybridized to Affymetrix GeneChip Mouse Genome 430.

Dataset Information

A role for Dicer in immune regulation

Publications

A role for Dicer in immune regulation.

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