MicroRNA-663 induces immune dysregulation by inhibiting TGF-β1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus

作     者：Linyu Geng Xiaojun Tang Kangxing Zhou Dandan Wang Shiying Wang Genhong Yao Weiwei Chen Xiang Gao Wanjun Chen Songtao Shi Nan Shen Xuebing Feng Lingyun Sun 

作者机构：Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Key Laboratory of Model Animal for Disease StudyModel Animal Research CenterNanjing UniversityNanjing 210000China Mucosal Immunology SectionOPCBNational Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesda 20892-2190MDUSA Department of Anatomy and Cell BiologySchool of Dental MedicineUniversity of PennsylvaniaPhiladelphia 19104-6004PAUSA Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji HospitalShanghai Institutes for Biological SciencesChinese Academy of Sciencesand Shanghai Jiaotong University School of MedicineShanghaiChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2019年第16卷第3期

页      面：260-274页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：by the Major International(Regional)Joint Research Project(No.81720108020) National Natural Science Foundation of China(No.81373199,81501347 and 81370730,81273304) National Natural Science Foundation of Jiangsu(BK20150098) Jiangsu Province Major Research and Development Program(BE2015602) Jiangsu Province 333 Talant Grant(BRA2016001) 

主　　题：immune dysregulation mesenchymal stem cells miR-663 systemic lupus erythematosus transforming growth factorβ1 

摘      要：Mesenchymal stem cells(MSCs)are critical for immune *** 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 ***,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 ***-663 inhibits the proliferation and migration of BMSCs and impairs BMSC-mediated downregulation of follicular T helper(Tfh)cells and upregulation of regulatory T(Treg)cells by targeting transforming growth factorβ1(TGF-β1).MiR-663 overexpression weakens the therapeutic effect of BMSCs,while miR-663 inhibition improves the remission of lupus disease in MRL/lpr ***,miR-663 is a key mediator of SLE BMSC regulation and may serve as a new therapeutic target for the treatment of lupus.