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Cell Mol Immunol. 2019 Mar;16(3):260-274. doi: 10.1038/cmi.2018.1. Epub 2018 Mar 26.

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

Author information

1
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
2
Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 210000, Nanjing, China.
3
Mucosal Immunology Section, OPCB, National Institute of Dental and Craniofacial Research, National Institutes of Health, 20892-2190, Bethesda, MD, USA.
4
Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, 19104-6004, Philadelphia, PA, USA.
5
Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai, China.
6
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China. fengxuebing@hotmail.com.
7
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China. lingyunsun@nju.edu.cn.

Abstract

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 (Tfh) cells and upregulation of regulatory T (Treg) 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.

PMID:
30886422
DOI:
10.1038/cmi.2018.1

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