MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3

Peripherally derived regulatory T (pT(reg)) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pT(reg)-cell generation. miR-31 conditional deletion results in enhanced induction of pT(reg) cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pT(reg-)cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pT(reg)-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional T(reg) cells in autoimmune diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:6

Enthalten in:

Nature communications - 6(2015) vom: 13. Juli, Seite 7639

Sprache:

Englisch

Beteiligte Personen:

Zhang, Lingyun [VerfasserIn]
Ke, Fang [VerfasserIn]
Liu, Zhaoyuan [VerfasserIn]
Bai, Jing [VerfasserIn]
Liu, Jinlin [VerfasserIn]
Yan, Sha [VerfasserIn]
Xu, Zhenyao [VerfasserIn]
Lou, Fangzhou [VerfasserIn]
Wang, Hong [VerfasserIn]
Zhu, Huiyuan [VerfasserIn]
Sun, Yang [VerfasserIn]
Cai, Wei [VerfasserIn]
Gao, Yuanyuan [VerfasserIn]
Li, Qun [VerfasserIn]
Yu, Xue-Zhong [VerfasserIn]
Qian, Youcun [VerfasserIn]
Hua, Zichun [VerfasserIn]
Deng, Jiong [VerfasserIn]
Li, Qi-Jing [VerfasserIn]
Wang, Honglin [VerfasserIn]

Links:

Volltext

Themen:

9007-81-2
Cytokines
Freund's Adjuvant
GPRC5A protein, mouse
Journal Article
MicroRNAs
Mirn31 microRNA, mouse
Receptors, Antigen, T-Cell
Receptors, G-Protein-Coupled
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 19.04.2016

Date Revised 30.03.2022

published: Electronic

GEO: GSE61938

Citation Status MEDLINE

doi:

10.1038/ncomms8639

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM250796120