Integrative Analysis of mRNA and miRNA Array Data Reveals the Suppression of Retinoic Acid Pathway in Regulatory T Cells of Graves' Disease
Integrative Analysis of mRNA and miRNA Array Data Reveals the Suppression of Retinoic Acid Pathway in Regulatory T Cells of Graves' Disease
复制标题
mRNA 和 miRNA 阵列数据的综合分析揭示了格雷夫斯病调节性 T 细胞中视黄酸途径的抑制
DOI：
10.1210/jc.2014-1883
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发表时间：
2014-12-01
影响因子：
5.8
通讯作者：
Zhang, Qunye
中科院分区：
文献类型：
--
作者：
Wang, Zhe;Fan, Xiaohua;Zhang, Qunye
背景：众所周知，格雷夫斯病 (GD) 中调节性 T 细胞 (Treg) 异常，在免疫耐受破坏和 GD 发展中发挥着至关重要的作用。然而，关于GD中Tregs的数量和/或功能是否异常仍存在争议。目前，Tregs异常的分子机制及其对GD发生的影响尚不清楚。 目的：miRNA在包括Tregs在内的免疫系统的功能和发育中发挥着重要作用。为了揭示GD中Tregs的异常及其分子机制，我们利用TaqMan miRNA阵列和mRNA微阵列系统研究了初诊GD患者Tregs的数量和免疫抑制功能以及miRNA和mRNA的差异表达谱。结果：我们的研究结果显示，初诊GD患者Tregs的数量和免疫抑制功能显着下降。更重要的是，视黄酸（RA）途径被显着抑制，其激动剂全反式视黄酸在体外可显着提高GD患者Tregs的数量和免疫抑制功能。此外，包括蛋白质泛素化和昼夜节律在内的许多其他途径也在GD的Tregs中受到显着调节。结论：这项综合研究首次揭示了GD初始Tregs中mRNA/miRNA的表达谱，RA途径可能在GD的发展中发挥重要作用。我们的结果表明，全反式RA在临床上已经使用了很长时间，在GD的治疗中具有潜在价值，值得进一步研究。
Context: It is well known that regulatory T cells (Tregs) are abnormal in Graves' disease (GD) and play crucial roles in the breakdown of immune tolerance and GD development. However, there are controversies about whether the quantity and/or function of Tregs is aberrant in GD. The molecular mechanism of Tregs abnormality and its effects on GD development was still unclear, until now.Objective: MiRNAs play important roles in the function and development of the immune system including Tregs. To reveal the Tregs abnormality and its molecular mechanism in GD, we systematically studied the quantity and immunosuppressive function as well as the differential expression profiles of miRNA and mRNA of Tregs in newly diagnosed patients with GD using TaqMan miRNA array and mRNA microarray.Results: Our results showed that the quantity and immunosuppressive function of Tregs in initial patients with GD was significantly decreased. More importantly, the retinoic acid (RA) pathway was markedly suppressed and its agonist, all-trans retinoic acid, could notably improve the quantity and immunosuppressive function of Tregs from patients with GD in vitro. In addition, many other pathways including protein ubiquitination and circadian rhythm were also significantly regulated in Tregs of GD.Conclusions: This integrative study first revealed the expression profiles of mRNA/miRNA in Tregs of initial GD and RA pathway might play important roles in GD development. Our results implied that all-trans RA, which had been used for a long time in the clinical setting, had potential value in the treatment of GD and was worthy of additional study.