Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Palermo, Italy.
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Palermo, Italy.
Arthritis Res Ther. 2018 Oct 22;20(1):236. doi: 10.1186/s13075-018-1740-7.
We aimed to evaluate the phenotype, function, and microRNA (miRNA)17-92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients.
Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17-92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied.
A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a T (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 T cells, and a lower level of miR-19b-3p among Vγ9Vδ2 T (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes.
Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17-92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.
我们旨在评估类风湿关节炎（RA）患者中 Vγ9Vδ2 T 细胞亚群的表型、功能和 miRNA（miR）17-92 簇表达，并分析其与免疫反应的相关性。
收集 10 例早期未经治疗的 RA 患者和 10 例健康供者（HD）外周血，体外诱导多克隆 Vγ9Vδ2 T 细胞系，并用流式细胞术进行分析。采用实时聚合酶链反应（RT-PCR）分析 miR17-92 簇表达，并研究 mRNA 靶基因的表达。
与 HD 相比，RA 患者外周血中 Vγ9Vδ2 T 细胞功能亚群的分布发生了显著变化，效应细胞亚群扩增，幼稚细胞减少，同时促炎细胞因子表达也发生了改变。具有 T（效应记忆）表型并产生促炎细胞因子的 Vγ9Vδ2 T 细胞与疾病活动评分（DAS28）相关。RA 患者和 HD 之间 Vγ9Vδ2 T 细胞亚群中 miRNA 表达的比较显示，Vγ9Vδ2 T 细胞中 miR-106a-5p 和 miR-20a-5p 水平较低，miR-21a-5p 水平较高，Vγ9Vδ2 T（中央记忆）细胞中 miR-19b-3p 水平较低。这些差异表达的 miRNA 与白细胞介素（IL）-8、IL-6 和 PDCD4 基因的高表达相关。
我们的研究结果为 miR-106a、miR-19-3p、miR-20a 和 miR-21a 在 RA 患者中调节 Vγ9Vδ2 T 细胞功能提供了证据，并提示 miR17-92 家族和 Vγ9Vδ2 T 细胞可能参与 RA 的发病机制。
