Presentation_1_Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus.pdf (80.53 kB)

Presentation_1_Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus.pdf

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posted on 18.02.2020 by Linyu Geng, Xiaojun Tang, Shiying Wang, Yue Sun, Dandan Wang, Betty P. Tsao, Xuebing Feng, Lingyun Sun

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 the imbalance of Treg/Th17 mediated by SLE BM-MSCs, suggesting the potential of manipulating let-7f expression in BM-MSCs for treating SLE patients.

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