Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation.
EMBO J. 34, 1195-1213 (2015)
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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
EMBO Journal, The
Quellenangaben
Band: 34,
Heft: 9,
Seiten: 1195-1213
Verlag
Wiley
Verlagsort
Heidelberg, Germany
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)
Institute of Pancreatic Islet Research (IPI)
Institute of Pancreatic Islet Research (IPI)