系统性红斑狼疮是一种以T细胞功能缺陷和B细胞过度活化及多种自身抗体产生为特点的自身免疫性疾病。已有的研究表明，I型干扰素的过度产生在系统性红斑狼疮的发病过程中起着十分重要的作用。它通过直接作用于T细胞和B细胞，促进自身免疫反应。因此，如何能够有效调控I型干扰素的产生，对于该自身免疫疾病的治疗有十分重要的意义。
配图来源：hhmi
近日，国际著名学术期刊《血液》在线发表了中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所分子风湿病学研究组的最新研究发现：来自于同一前体的miR-155和miR-155*协同调控浆细胞样树突状细胞（pDC）I型干扰素的产生。
近年来，microRNA作为一种非编码RNA分子，被证明在免疫调节的各个方面均有很重要的作用。因此，在沈南教授的指导下，整合中国科学院上海生命科学研究院健康科学研究所的基础研究力量和上海交通大学附属仁济医院风湿科的临床优势，周海波和黄新芳等深入研究了microRNA 在I型干扰素主要产生细胞――浆细胞样树突状细胞（pDC）中的调控作用。
该研究发现，pDC激活后伴随着大量I型干扰素的产生，miR-155*和miR-155分别在不同的时间被显着诱导。MiR-155*主要在早期被诱导，而miR-155则主要在刺激的后期被诱导。进一步研究表明，miR-155*通过靶向IRAKM，促进I型干扰素的产生，而miR-155通过靶向TAB2，抑制I型干扰素的产生。这些结果表明，它们在pDC活化的不同阶段协同发挥作用。此外，通过对miR-155和miR-155*产生机制的研究，发现pDC自身分泌的I型干扰素以及被激活的KHSRP蛋白可以在转录后水平反向调控miR-155和miR-155*的产生，这一结果解释了来自于同一前体的miR-155*和miR-155却能在不同的时间点被诱导的原因。
该研究不仅揭示了来自于同一前体microRNA和microRNA*的产生，在同一刺激过程中可以被精确调控，从而使它们能够协同调控这一过程，而且阐明了新的有效调控I型干扰素产生的机制，为系统性红斑狼疮疾病的的治疗提供了新的理论依据和潜在靶点。
该项工作得到国家科技部、国家自然科学基金和上海市科委的经费支持。（生物谷Bioon.com）
生物谷推荐英文摘要：
Blood 2010; DOI 10.1182/blood-2010-04-280156.
miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells
Haibo Zhou1, Xinfang Huang1, Huijuan Cui1, Xiaobing Luo1, Yuanjia Tang1, Shunle Chen1, Li Wu2 and Nan Shen1,*
Haibo Zhou1, Xinfang Huang1, Huijuan Cui1, Xiaobing Luo1, Yuanjia Tang1, Shunle Chen1, Li Wu2 and Nan Shen1,*
The recent discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation, affecting the immune system. Here, we identify their roles in regulating human plasmacytoid dendritic cell (PDC) activation. miRNA profiling showed the significantly differential expression of 19 miRNAs in PDCs after Toll-like receptor 7 (TLR7) stimulation, among which miR-155* and miR-155 were most highly induced. Although they were processed from a single precursor and were both induced by TLR7 through the JNK pathway, miR-155* and miR-155 had opposite effects on the regulation of type I interferon (type I IFN) production by PDC. Further study indicated that miR-155* augmented interferon /β (IFN/β) expression by suppressing IRAKM, whereas miR-155 inhibited their expression by targeting TAB2. Kinetic analysis of miR-155* and miR-155 induction revealed that miR-155* was mainly induced in the early stage of stimulation and that miR-155 was mainly induced in the later stage, suggesting their cooperative involvement in PDC activation. Finally, we demonstrated that miR-155* and miR-155 were inversely regulated by autocrine/paracrine type I IFN and TLR7-activated KHSRP at posttranscriptional level, which led to their different dynamic induction by TLR7. Thus, our study identified and validated novel miRNA-protein networks involved in regulating PDC activation.
