RGD Reference Report - Adenovirus-mediated down-regulation of miR-21-5p alleviates experimental autoimmune uveoretinitis in mice. - Rat Genome Database

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Adenovirus-mediated down-regulation of miR-21-5p alleviates experimental autoimmune uveoretinitis in mice.

Authors: Shi, Long  Guo, Hui  Li, Ziwei  Wang, Yuwei  Wang, Yuanjian  Cui, Yan 
Citation: Shi L, etal., Int Immunopharmacol. 2019 Sep;74:105698. doi: 10.1016/j.intimp.2019.105698. Epub 2019 Jun 19.
RGD ID: 41404699
Pubmed: (View Article at PubMed) PMID:31228813
DOI: Full-text: DOI:10.1016/j.intimp.2019.105698

MiR-21-5p has been found to be up-regulated in the retina of experimental autoimmune uveoretinitis (EAU) mice and correlated with the pathogenesis of EAU. The objective of the present study is to explore the role of miR-21-5p in EAU. C57 mice were immunized with residue1-20 (IRBP1-20) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis H37Ra to induce EAU, and miR-21-5p was knocked down via subretinal injection of anti-miR-21-5p adenovirus. The pathological score, TUNEL positive cells and the expression of pro-inflammatory factors in the retina were reduced, and the expression of IL-10 was increased by down-regulation of miR-21-5p. Up-regulation of miR-21-5p significantly decreased the mRNA and protein levels of IL-10 in ARPE-19 cells. The binding activity of miR-21-5p on the 3'UTR of IL-10 mRNA was confirmed by luciferase reporter assay. Moreover, the miR-21-5p level in splenic lymphocytes of EAU mice was increased at the 7th day after immunization and reached its peak at the 14th day, that was in accordance with the changing trend with the Th17 cell frequency in the spleen. Besides, lentivirus-mediated down-regulation of miR-21-5p reduced the Th17 cell frequency and increased the Treg cell fraction of IRBP1-20-stimulated lymphocytes in vitro. Taken together, in situ down-regulation of miR-21-5p attenuates EAU by inhibiting inflammatory responses and reducing retinal cell apoptosis. miR-21-5p may also participate in the progress of EAU by affecting Th17/Treg balance via the regulation of IL-10. Therefore, we demonstrate that miR-21-5p can serve as a therapeutic target in the management of uveitis and other autoimmune diseases.

Disease Annotations    
autoimmune uveitis  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)

Additional Information