系統(tǒng)性紅斑狼瘡是一種以T細胞功能缺陷和B細胞過度活化及多種自身抗體產生為特點的自身免疫性疾病,。已有的研究表明,，I型干擾素的過度產生在系統(tǒng)性紅斑狼瘡的發(fā)病過程中起著十分重要的作用。它通過直接作用于T細胞和B細胞,，促進自身免疫反應,。因此，如何能夠有效調控I型干擾素的產生,，對于該自身免疫疾病的治療有十分重要的意義。
配圖來源：hhmi
近日,，國際著名學術期刊《血液》在線發(fā)表了中國科學院上海生命科學研究院/上海交通大學醫(yī)學院健康科學研究所分子風濕病學研究組的最新研究發(fā)現(xiàn)：來自于同一前體的miR-155和miR-155*協(xié)同調控漿細胞樣樹突狀細胞（pDC）I型干擾素的產生,。
近年來，microRNA作為一種非編碼RNA分子,，被證明在免疫調節(jié)的各個方面均有很重要的作用,。因此，在沈南教授的指導下,，整合中國科學院上海生命科學研究院健康科學研究所的基礎研究力量和上海交通大學附屬仁濟醫(yī)院風濕科的臨床優(yōu)勢,，周海波和黃新芳等深入研究了microRNA 在I型干擾素主要產生細胞——漿細胞樣樹突狀細胞（pDC）中的調控作用。
該研究發(fā)現(xiàn),，pDC激活后伴隨著大量I型干擾素的產生,，miR-155*和miR-155分別在不同的時間被顯著誘導。MiR-155*主要在早期被誘導,，而miR-155則主要在刺激的后期被誘導,。進一步研究表明，miR-155*通過靶向IRAKM,，促進I型干擾素的產生,，而miR-155通過靶向TAB2，抑制I型干擾素的產生,。這些結果表明,，它們在pDC活化的不同階段協(xié)同發(fā)揮作用。此外,，通過對miR-155和miR-155*產生機制的研究,，發(fā)現(xiàn)pDC自身分泌的I型干擾素以及被激活的KHSRP蛋白可以在轉錄后水平反向調控miR-155和miR-155*的產生，這一結果解釋了來自于同一前體的miR-155*和miR-155卻能在不同的時間點被誘導的原因,。
該研究不僅揭示了來自于同一前體microRNA和microRNA*的產生,，在同一刺激過程中可以被精確調控，從而使它們能夠協(xié)同調控這一過程,，而且闡明了新的有效調控I型干擾素產生的機制,，為系統(tǒng)性紅斑狼瘡疾病的的治療提供了新的理論依據(jù)和潛在靶點。
該項工作得到國家科技部,、國家自然科學基金和上海市科委的經(jīng)費支持,。（生物谷Bioon.com）
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生物谷推薦英文摘要：
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.
