Cell Physiol Biochem：研究人员发现外泌体miRNA参与调节风湿性关节...

生物_医药_科研 2018-12-19

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循环调节性T细胞（Tregs）的降低是类风湿性关节炎（rheumatoid arthritis，RA）的炎症标志之一，后者是最常见的自身免疫疾病类型。其特征在于滑膜炎症、自身抗体如抗瓜氨酸化蛋白抗体（Ab）的产生、以及软骨和骨的破坏。

近日，最新研究发现RA患者中的循环外泌体miRNA表达会发生改变，早期活动性RA患者中循环CD4⁺CD25⁺ Treg的比例降低，Tregs抑制促炎细胞因子产生，并且TNF依赖的Tregs对增殖效应细胞的抑制作用降低。然而，人们对Tregs这种改变的潜在机制尚不清楚。微小RNA（miRNA）是一种小内源性非编码RNA，通过与其靶mRNA的互补反义结合负调节基因表达。研究人员在炎症细胞或自身免疫疾病的病理样本中均发现循环miRNA的改变。miRNA存在于外泌体中，外泌体可以通过基因调控影响靶细胞。

在这项新的研究中，研究人员从RA患者的血液中分离出循环外泌体，评估了这些含有miRNA的外泌体在Treg分化中的潜在致病功能。结果发现RA外泌体可以在体外选择性地影响Tregs。RA外泌体中的几种miRNA比来自健康对照供体的外泌体中丰度更高。在RA患者中上调的miRNA中，miR-17可通过抑制转化生长因子β受体II（TGFBRII）的表达来抑制Treg诱导。该研究表明，RA外泌体中miRNA表达的改变可能通过调节Tregs的体内平衡影响RA的发生，为风湿性关节炎的诊断提供了潜在靶标。

推荐阅读原文：
Circulating Exosomal miR-17 Inhibits the Induction of Regulatory T Cells via Suppressing TGFBR II Expression in Rheumatoid Arthritis.
BACKGROUND/AIMS:
A reduced prevalence of circulating regulatory T cells (Tregs)is a hallmark of inflammatory rheumatoid arthritis (RA). However, the underlying mechanisms of alterations of Tregs are unclear.
METHODS:
The ratio of Tregs in peripheral blood of healthy controls (HCs) and patients with RA was determined by flow cytometry. MicroRNA (miRNA) expression profiles in exosomes derived from RA patients (RA-exosomes) and in those from HCs (HC-exosomes) were detected by microarray analysis, and miR-17 was measured by quantitative real-time PCR. Transforming growth factor beta receptor II (TGFBR II) expressed by T cells was measured by flow cytometry. The interaction between miR-17 and TGFBR II was evaluated by dual-luciferase reporter assay.
RESULTS:
We found that RA-exosomes can selectively affect Treg differentiation in vitro. Several miRNAs are more abundant in the RA-exosomes than in HC-exosomes. Among those upregulated in patients with RA, miR-17 can suppress Treg induction by inhibiting the expression of TGFBR II.
CONCLUSION:
Our findings imply that altered miRNA expression in RA-exosomes may contribute to the pathogenesis of RA by disrupting the homeostasis of Tregs.