@article {Changbjophthalmol-2017-311079, author = {Rui Chang and Shenglan Yi and Xiao Tan and Yang Huang and Qingfeng Wang and Guannan Su and Chunjiang Zhou and Qingfeng Cao and Gangxiang Yuan and Aize Kijlstra and Peizeng Yang}, title = {MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease}, elocation-id = {bjophthalmol-2017-311079}, year = {2017}, doi = {10.1136/bjophthalmol-2017-311079}, publisher = {BMJ Publishing Group Ltd}, abstract = {Aim To elucidate the role of microRNA-20a-5p (miR-20a-5p) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.Methods Quantitative real-time 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. 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.Results The 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 pathway.Conclusions Our 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.}, issn = {0007-1161}, URL = {https://bjo.bmj.com/content/early/2017/09/28/bjophthalmol-2017-311079}, eprint = {https://bjo.bmj.com/content/early/2017/09/28/bjophthalmol-2017-311079.full.pdf}, journal = {British Journal of Ophthalmology} }