MicroRNA-663 Induces Immune Dysregulation by Inhibiting TGF-β1 Production in Bone Marrow-derived Mesenchymal Stem Cells in Patients with Systemic Lupus Erythematosus

Overview

Journal Cell Mol Immunol

Date 2019 Mar 20

PMID 30886422

Citations 38

Authors

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

Affiliations

Soon will be listed here.

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 (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.

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