MicroRNA-20a-5p Suppresses IL-17 Production By Targeting OSM And CCL1 In Patients With Vogt-koyanagi-harada Disease

Background and purposeUveitis is a common autoimmune eye disease with a high rate of blinding.In China,Vogt-Koyanagi-Harada(VKH)syndrome is a common type of uveitis.However,the mechanisms responsible for the onset and progression remain unclear.MicroRNAs(miRNAs)are small,non-coding RNAs that bind to the 3’ untranslated region(3’ UTR)of the coding gene mRNA through the base-pairing and participate in post-transcriptional regulation of gene expression.It has been shown that MicroRNA-20a-5p(miR-20a-5p)is involved in the regulation of the pathogenesis and progression of multiple sclerosis(MS)diseases,suggesting that miR-20a-5p might regulate the progression of autoimmune disease.Therefore,we speculated that miR-20a-5p was also involved in the regulation of the pathogenesis and progression of VKH syndrome.This study was to investigate the role and mechanism of miR-20a-5p in VKH syndrome,and reveal a new miRNA regulating VKH syndrome and provide new ideas for understanding the pathogenesis and progression of the disease.MethodsQuantitative real-time PCR(qRT-PCR)was used to quantify miR-20a-5p expression in CD4+T cells from patients with active VKH and normal controls.The promoter methylation status of miR-20a-5p was detected by bisulfite sequencing PCR(BSP).Targets were evaluated by a luciferase reporter assay.The functional effects of miR-20a-5p on CD4+T cells from patients with active VKH were assessed by upregulation or downregulation of its expression using liposomes.ResultsThe miR-20a-5p level was significantly decreased in CD4+T cells from patients with active VKH as compared with normal controls.The two genes,oncostatin M(OSM)and C-C motif chemokine ligand 1(CCL1),were identified as targets of miR-20a-5p.The upregulation of miR-20a-5p significantly suppressed interleukin 17(IL-17)production in CD4+T cells from patients with active VKH,whereas downregulation of miR-20a-5p exhibited an inverse effect.In addition,overexpression of OSM and CCL1 could rescue the effect of the upregulation of miR-20a-5p.Moreover,the level of miR-20a-5p was reduced in response to hypermethylation of the promoter.Further study showed that miR-20a-5p suppressed the activity of the phosphoinositide 3-kinase-AKT(PI3K-AKT)pathway.ConclusionsOur findings indicate that downregulation of miR-20a-5p is caused by promoter hypermethylation.MiR-20a-5p could also suppress the production of IL-17 by targeting OSM and CCL1 production in CD4+T cells in patients with active VKH.