Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
Eur J Immunol. 2013 Jan;43(1):104-14. doi: 10.1002/eji.201242702. Epub 2012 Nov 29.
MicroRNAs (miRNAs) play important roles in the regulation of immune responses. There is evidence that miRNAs also participate in the pathogenesis of multiple sclerosis (MS), but how the miRNAs regulate the pathogenesis of MS is still under investigation. The identification of new members of the miRNA family associated with the pathogenesis of MS could facilitate early diagnosis and treatment. Here, we show that the level of miRNA let-7e is significantly upregulated in EAE, an animal model of MS using miRNA array and quantitative real-time PCR. The expression of let-7e was mainly in CD4(+) T cells and infiltrated mononuclear cells of CNS, and highly correlated with the development of EAE. We found that let-7e silencing in vivo inhibited encephalitogenic Th1 and Th17 cells and attenuated EAE, with reciprocal increase of Th2 cells; overexpression of let-7e enhanced Th1 and Th17 cells and aggravated EAE. We also identified IL-10 as one of the functional targets of let-7e. Together, we propose that let-7e is a new miRNA involved in the regulation of encephalitogenic T-cell differentiation and the pathogenesis of EAE.
MicroRNAs (miRNAs) 在免疫反应的调节中发挥重要作用。有证据表明，miRNAs 也参与多发性硬化症 (MS) 的发病机制，但 miRNA 如何调节 MS 的发病机制仍在研究中。鉴定与 MS 发病机制相关的新 miRNA 成员可能有助于早期诊断和治疗。在这里，我们通过 miRNA 阵列和定量实时 PCR 显示，EAE（MS 的动物模型）中 miRNA let-7e 的水平显著上调。let-7e 的表达主要在 CD4(+) T 细胞和 CNS 浸润的单核细胞中，与 EAE 的发展高度相关。我们发现体内 let-7e 沉默抑制致脑炎 Th1 和 Th17 细胞并减轻 EAE，同时 Th2 细胞增加；let-7e 的过表达增强 Th1 和 Th17 细胞并加重 EAE。我们还鉴定出 IL-10 是 let-7e 的功能靶标之一。总之，我们提出 let-7e 是一种新的 miRNA，参与调节致脑炎 T 细胞分化和 EAE 的发病机制。
