A role for Dicer in immune regulation

Author:

Cobb Bradley S.1,Hertweck Arnulf1,Smith James2,O'Connor Eric3,Graf Daniel4,Cook Terence5,Smale Stephen T.6,Sakaguchi Shimon7,Livesey Frederick J.28,Fisher Amanda G.1,Merkenschlager Matthias1

Affiliation:

1. Lymphocyte Development Group,

2. Wellcome Trust/CRUK Gurdon Institute and

3. Flow Cytometry Facility, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK

4. Institute of Immunology, Biomedical Sciences Research Center “Al. Fleming,” 166 72 Vari, Greece

5. Division of Investigative Sciences, and

6. Department of Microbiology, Immunology, and Molecular Genetics, and Molecular Biology Institute, University of California, Los Angeles, CA 90095

7. Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8501, Japan

8. Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, England, UK

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 β. These results suggest that T reg cell development involves Dicer-generated RNAs.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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