PuSH - Publication Server of Helmholtz Zentrum München: Induced miR-99a expression represses <em>Mtor</em> cooperatively with miR-150 to promote regulatory T-cell differentiation.

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Warth, S.C. ; Höfig, K.P. ; Hiekel, A. ; Schallenberg, S.* ; Jovanovic, K.* ; Klein, L.* ; Kretschmer, K.* ; Ansel, K.M.* ; Heissmeyer, V.

Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation.

EMBO J. 34, 1195-1213 (2015)

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Open Access Green as soon as Postprint is submitted to ZB.

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Peripheral induction of regulatory T (Treg) cells provides essential protection from inappropriate immune responses. CD4(+) T cells that lack endogenous miRNAs are impaired to differentiate into Treg cells, but the relevant miRNAs are unknown. We performed an overexpression screen with T-cell-expressed miRNAs in naive mouse CD4(+) T cells undergoing Treg differentiation. Among 130 candidates, the screen identified 29 miRNAs with a negative and 10 miRNAs with a positive effect. Testing reciprocal Th17 differentiation revealed specific functions for miR-100, miR-99a and miR-10b, since all of these promoted the Treg and inhibited the Th17 program without impacting on viability, proliferation and activation. miR-99a cooperated with miR-150 to repress the expression of the Th17-promoting factor mTOR. The comparably low expression of miR-99a was strongly increased by the Treg cell inducer "retinoic acid", and the abundantly expressed miR-150 could only repress Mtor in the presence of miR-99a. Our data suggest that induction of Treg cell differentiation is regulated by a miRNA network, which involves cooperation of constitutively expressed as well as inducible miRNAs.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Treg Cells ; T‐cell Differentiation ; Mirna Function; Transcription Factor Foxp3; Microrna Target Sites; Tgf-beta; Lineage Differentiation; Messenger-rnas; Retinoic Acid; Th1 Responses; Reg-cells; Ror-gamma; Dicer

ISSN (print) / ISBN 0261-4189

e-ISSN 1460-2075

Journal EMBO Journal, The

Quellenangaben Volume: 34, Issue: 9, Pages: 1195-1213

Publisher Wiley

Publishing Place Heidelberg, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Immunology (IMI)
Institute of Pancreatic Islet Research (IPI)