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.
Duke Scholars
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Related Subject Headings
- T-Lymphocytes, Regulatory
- Spinal Cord
- Signal Transduction
- Reverse Transcriptase Polymerase Chain Reaction
- Receptors, G-Protein-Coupled
- Receptors, Antigen, T-Cell
- Real-Time Polymerase Chain Reaction
- MicroRNAs
- Mice, Knockout
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- T-Lymphocytes, Regulatory
- Spinal Cord
- Signal Transduction
- Reverse Transcriptase Polymerase Chain Reaction
- Receptors, G-Protein-Coupled
- Receptors, Antigen, T-Cell
- Real-Time Polymerase Chain Reaction
- MicroRNAs
- Mice, Knockout
- Mice