微小 RNA-663 通过抑制系统性红斑狼疮患者骨髓间充质干细胞产生 TGF-β1 诱导免疫失调。
MicroRNA-663 induces immune dysregulation by inhibiting TGF-β1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus.
机构信息
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 210000, Nanjing, China.
出版信息
Cell Mol Immunol. 2019 Mar;16(3):260-274. doi: 10.1038/cmi.2018.1. Epub 2018 Mar 26.
Mesenchymal stem cells (MSCs) are critical for immune regulation. Although several microRNAs (miRNAs) have been shown to participate in autoimmune pathogenesis by affecting lymphocyte development and function, the roles of miRNAs in MSC dysfunction in autoimmune diseases remain unclear. Here, we show that patients with systemic lupus erythematosus (SLE) display a unique miRNA signature in bone marrow-derived MSCs (BMSCs) compared with normal controls, among which miR-663 is closely associated with SLE disease activity. MiR-663 inhibits the proliferation and migration of BMSCs and impairs BMSC-mediated downregulation of follicular T helper (T) cells and upregulation of regulatory T (T) cells by targeting transforming growth factor β1 (TGF-β1). MiR-663 overexpression weakens the therapeutic effect of BMSCs, while miR-663 inhibition improves the remission of lupus disease in MRL/lpr mice. Thus, miR-663 is a key mediator of SLE BMSC regulation and may serve as a new therapeutic target for the treatment of lupus.
间充质干细胞（MSCs）对于免疫调节至关重要。尽管已经有几种 microRNAs（miRNAs）通过影响淋巴细胞的发育和功能参与自身免疫发病机制，但 miRNAs 在自身免疫性疾病中 MSC 功能障碍中的作用仍不清楚。在这里，我们发现与正常对照相比，系统性红斑狼疮（SLE）患者骨髓来源的间充质干细胞（BMSCs）中存在独特的 miRNA 特征，其中 miR-663 与 SLE 疾病活动密切相关。miR-663 通过靶向转化生长因子 β1（TGF-β1）抑制 BMSCs 的增殖和迁移，并损害 BMSC 介导的滤泡辅助性 T 细胞（Tfh）下调和调节性 T（Treg）细胞上调。miR-663 的过表达削弱了 BMSCs 的治疗效果，而 miR-663 的抑制则改善了 MRL/lpr 小鼠狼疮疾病的缓解。因此，miR-663 是 SLE BMSC 调节的关键介质，可能成为治疗狼疮的新治疗靶点。
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