Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus.

Frontiers in Immunology
Linyu GengLingyun Sun

Abstract

Systemic lupus erythematosus (SLE) patients exist an imbalance between regulatory T (Treg) and T helper 17 cells (Th17), which might be contributed by defective immune regulation of bone marrow derived mesenchymal stem cells (BM-MSCs) from SLE patients. Our microRNA array analysis showed markedly down-regulated expression levels of microRNA let-7f in BM-MSCs from SLE patients compared to those from normal controls (NOR). To explore the role of let-7f in the disease pathogenesis, we showed that expression levels of let-7f in SLE BM-MSCs were negatively associated with SLE disease activity, and the predicted let-7 family targeted gene expression of interlukin-6 (IL-6) was significantly higher in BM-MSCs from SLE patients compared to normal controls (NOR). Transient transfection of BM-MSCs with let-7f mimics or inhibitors showed reduced levels of let-7f impaired the proliferation rate of BM-MSCs, BM-MSC-mediated downregulation of Th17 cells and upregulation of Treg cells, increased the apoptosis rate of BM-MSCs through targeting IL-6 and activating signal transducers and activators of transcription-3 (STAT3) pathway, but had no significant effect on the differentiation of Th1 and Th2. Our findings showed a key role of let-7f in th...Continue Reading

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Citations

Jul 28, 2020·EMBO Molecular Medicine·Eliise Laura NirkMario Mauthe
Aug 20, 2020·Stem Cell Research & Therapy·Lei ShuGanzhu Feng
Jun 26, 2020·Biomolecules·Mohammad TaheriSoudeh Ghafouri-Fard
May 28, 2021·Frontiers in Cell and Developmental Biology·Fabian Vega-TapiaLoreto Cuitino
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Xinyi LvXiangmei Chen
Jul 30, 2021·Cellular & Molecular Immunology·Linyu Geng, Lingyun Sun
Aug 5, 2021·Nature Reviews. Rheumatology·Mélissa Noack, Pierre Miossec

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Methods Mentioned

BETA
transfection
ELISA
flow cytometry
Assay
electrophoresis
PCR
Enzyme-Linked Immunosorbent Assay

Software Mentioned

GraphPad Prism
Target Scan program
Flowjo
Targetscan
PITA

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