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 |
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Erscheinungsjahr: |
2015 |
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Erschienen: |
2015 |
Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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Enthalten in: |
Nature communications - 6(2015) vom: 13. Juli, Seite 7639 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Lingyun [VerfasserIn] |
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Links: |
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Themen: |
9007-81-2 |
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Anmerkungen: |
Date Completed 19.04.2016 Date Revised 30.03.2022 published: Electronic GEO: GSE61938 Citation Status MEDLINE |
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doi: |
10.1038/ncomms8639 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM250796120 |
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520 | |a 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 | ||
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700 | 1 | |a Bai, Jing |e verfasserin |4 aut | |
700 | 1 | |a Liu, Jinlin |e verfasserin |4 aut | |
700 | 1 | |a Yan, Sha |e verfasserin |4 aut | |
700 | 1 | |a Xu, Zhenyao |e verfasserin |4 aut | |
700 | 1 | |a Lou, Fangzhou |e verfasserin |4 aut | |
700 | 1 | |a Wang, Hong |e verfasserin |4 aut | |
700 | 1 | |a Zhu, Huiyuan |e verfasserin |4 aut | |
700 | 1 | |a Sun, Yang |e verfasserin |4 aut | |
700 | 1 | |a Cai, Wei |e verfasserin |4 aut | |
700 | 1 | |a Gao, Yuanyuan |e verfasserin |4 aut | |
700 | 1 | |a Li, Qun |e verfasserin |4 aut | |
700 | 1 | |a Yu, Xue-Zhong |e verfasserin |4 aut | |
700 | 1 | |a Qian, Youcun |e verfasserin |4 aut | |
700 | 1 | |a Hua, Zichun |e verfasserin |4 aut | |
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700 | 1 | |a Li, Qi-Jing |e verfasserin |4 aut | |
700 | 1 | |a Wang, Honglin |e verfasserin |4 aut | |
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