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循環(huán)調(diào)節(jié)性T細(xì)胞（Tregs）的降低是類風(fēng)濕性關(guān)節(jié)炎（rheumatoid arthritis，RA）的炎癥標(biāo)志之一，后者是最常見的自身免疫疾病類型。其特征在于滑膜炎癥、自身抗體如抗瓜氨酸化蛋白抗體（Ab）的產(chǎn)生、以及軟骨和骨的破壞。

近日，最新研究發(fā)現(xiàn)RA患者中的循環(huán)外泌體miRNA表達(dá)會發(fā)生改變，早期活動性RA患者中循環(huán)CD4⁺CD25⁺ Treg的比例降低，Tregs抑制促炎細(xì)胞因子產(chǎn)生，并且TNF依賴的Tregs對增殖效應(yīng)細(xì)胞的抑制作用降低。然而，人們對Tregs這種改變的潛在機(jī)制尚不清楚。微小RNA（miRNA）是一種小內(nèi)源性非編碼RNA，通過與其靶mRNA的互補(bǔ)反義結(jié)合負(fù)調(diào)節(jié)基因表達(dá)。研究人員在炎癥細(xì)胞或自身免疫疾病的病理樣本中均發(fā)現(xiàn)循環(huán)miRNA的改變。miRNA存在于外泌體中，外泌體可以通過基因調(diào)控影響靶細(xì)胞。

在這項(xiàng)新的研究中，研究人員從RA患者的血液中分離出循環(huán)外泌體，評估了這些含有miRNA的外泌體在Treg分化中的潛在致病功能。結(jié)果發(fā)現(xiàn)RA外泌體可以在體外選擇性地影響Tregs。RA外泌體中的幾種miRNA比來自健康對照供體的外泌體中豐度更高。在RA患者中上調(diào)的miRNA中，miR-17可通過抑制轉(zhuǎn)化生長因子β受體II（TGFBRII）的表達(dá)來抑制Treg誘導(dǎo)。該研究表明，RA外泌體中miRNA表達(dá)的改變可能通過調(diào)節(jié)Tregs的體內(nèi)平衡影響RA的發(fā)生，為風(fēng)濕性關(guān)節(jié)炎的診斷提供了潛在靶標(biāo)。

推薦閱讀原文：
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.