Xia Yuan, Tao Jin-Hui, Fang Xuan, Xiang Nan, Dai Xiao-Juan, Jin Li, Li Xiao-Mei, Wang Yi-Ping, Li Xiang-Pei
Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated with Anhui Medical University, Hefei 230001, China.
Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Mol Ther Nucleic Acids. 2018 Jun 1;11:284-291. doi: 10.1016/j.omtn.2018.02.010. Epub 2018 Mar 1.
B cells are recognized as key participants in various autoimmune diseases, including systemic lupus erythematosus (SLE). Although sets of transcription factors and cytokines are known to regulate B cell differentiation, the roles of microRNAs are poorly understood. Our previous study proved that microRNA-326 (miR-326) was markedly upregulated in SLE patients; however, the biological function of miR-326 during SLE pathogenesis remained unknown. In this study, we found that miR-326 overexpression in MRL/lpr mice led to B cell hyperactivity and severe SLE. Moreover, E26 transformation-specific-1 (Ets-1), a negative regulator of B cell differentiation, was identified as a target of miR-326. Therefore, a novel mechanism has been found in which the elevated miR-326 in B cells of SLE promotes plasmablast development and antibody production through downregulation of Ets-1.
B细胞被认为是包括系统性红斑狼疮（SLE）在内的各种自身免疫性疾病的关键参与者。尽管已知有一系列转录因子和细胞因子可调节B细胞分化，但对微小RNA的作用却了解甚少。我们之前的研究证明，微小RNA - 326（miR - 326）在SLE患者中显著上调；然而，miR - 326在SLE发病机制中的生物学功能仍不清楚。在本研究中，我们发现MRL/lpr小鼠中miR - 326过表达导致B细胞活性亢进和严重的SLE。此外，E26转化特异性-1（Ets - 1）作为B细胞分化的负调节因子，被确定为miR - 326的一个靶点。因此，发现了一种新机制，即SLE患者B细胞中升高的miR - 326通过下调Ets - 1促进浆母细胞发育和抗体产生。
