Effects of Plasma-Derived Exosomal miRNA-19b-3p on Treg/T Helper 17 Cell Imbalance in Behcet's Uveitis

作者全名："Jiang, Qingyan; Wang, Qingfeng; Tan, Shiyao; Cai, Jinyu; Ye, Xingsheng; Su, Guannan; Yang, Peizeng"

作者地址："[Jiang, Qingyan; Wang, Qingfeng; Tan, Shiyao; Cai, Jinyu; Ye, Xingsheng; Su, Guannan; Yang, Peizeng] Chongqing Med Univ, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Chongqing, Peoples R China; [Yang, Peizeng] Chongqing Med Univ, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Youyi Rd 1, Chongqing 400016, Peoples R China"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Youyi Rd 1, Chongqing 400016, Peoples R China."

来源：INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001039109200008

JCR分区：Q1

影响因子：5

年份：2023

卷号：64

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Behcet's uveitis; plasma exosomes; miR-19b-3p; CD46; Treg; Th17 cell imbalance

摘要："PURPOSE. To explore the potential role of plasma-derived exosomal microRNAs (miRNAs) in the development of regulatory T cell (Treg)/T helper 17 (Th17) cell imbalances in Behcet's uveitis (BU). METHODS. The exosome treatment was conducted to evaluate the effects of plasma exosomes from patients with active BU and healthy controls on the Treg/Th17 cell balance. miRNA sequencing analysis of plasma exosomes was conducted to identify differentially expressed miRNAs between patients with active BU and healthy controls. miRTarBase analysis and dual-luciferase reporter assays were conducted to identify the target genes of miR-19b-3p. CD4+T cells were transfected with miR-19b-3p mimic or inhibitor to evaluate its regulation of the Treg/Th17 cell balance. The Treg/Th17 cell balance in CD4+T cells was evaluated by flow cytometry and enzyme-linked immunosorbent assay. RESULTS. Exosomes from patients with active BU promoted Th17 cell differentiation and inhibited Treg cell differentiation. MiRNA sequencing analysis revealed 177 upregulated and 274 downregulated miRNAs in plasma exosomes of patients with active BU. Among them, miR-19b-3p was significantly elevated, and its target genes were identified as being involved in T-cell differentiation. miR-19b-3p overexpression downregulated CD46 expression and the Treg/Th17 cell ratio in CD4+T cells from healthy controls, whereas miR-19b-3p inhibition reversed these regulatory effects and restored the Treg/Th17 cell balance of CD4+T cells from patients with active BU. CONCLUSIONS. Plasma-derived exosomes from patients with active BU showed a markedly differential miRNA expression in comparison to healthy controls. Highly expressed miRNA-19b-3p could induce a Treg/Th17 cell imbalance, probably by downregulating CD46 expression."

基金机构："National Natural Science Foundation Key Program [81930023, 82230032]; Key Project of Chongqing Science and Technology Bureau [CSTC2021jscx-gksb-N0010]; National Natural Science Foundation [82101106]; Natural Science Foundation of Chongqing [cstc2021jcyj-bsh0055]; Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]; Chongqing Science amp; Technology Platform and Base Construction Program [cstc2014pt-sy10002]; Chongqing Outstanding Scientists Project (2019)"

基金资助正文："Supported by grants from the National Natural Science Foundation Key Program (82230032), National Natural Science Foundation Key Program (81930023), Key Project of Chongqing Science and Technology Bureau (CSTC2021jscx-gksb-N0010), National Natural Science Foundation (82101106), Chongqing Outstanding Scientists Project (2019), Natural Science Foundation of Chongqing (cstc2021jcyj-bsh0055), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), and the Chongqing Science & amp; Technology Platform and Base Construction Program (cstc2014pt-sy10002)."