Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus
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 do...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00233/full |
| _version_ | 1818040191532662784 |
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| author | Linyu Geng Linyu Geng Xiaojun Tang Shiying Wang Yue Sun Dandan Wang Betty P. Tsao Xuebing Feng Lingyun Sun |
| author_facet | Linyu Geng Linyu Geng Xiaojun Tang Shiying Wang Yue Sun Dandan Wang Betty P. Tsao Xuebing Feng Lingyun Sun |
| author_sort | Linyu Geng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T08:10:36Z |
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| id | doaj.art-e6b97d576b68470fa3f9faa1a72cce7b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T08:10:36Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e6b97d576b68470fa3f9faa1a72cce7b2022-12-22T01:56:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00233477718Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus ErythematosusLinyu Geng0Linyu Geng1Xiaojun Tang2Shiying Wang3Yue Sun4Dandan Wang5Betty P. Tsao6Xuebing Feng7Lingyun Sun8Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDivision of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDivision of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, United StatesDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaSystemic 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.00233/fulllet-7f miRNAsystemic lupus erythematosusbone marrow derived mesenchymal stem cellinterlukin 6regulatory T cell (Treg)T help cell 17 (Th17) |
| spellingShingle | Linyu Geng Linyu Geng Xiaojun Tang Shiying Wang Yue Sun Dandan Wang Betty P. Tsao Xuebing Feng Lingyun Sun Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus Frontiers in Immunology let-7f miRNA systemic lupus erythematosus bone marrow derived mesenchymal stem cell interlukin 6 regulatory T cell (Treg) T help cell 17 (Th17) |
| title | Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus |
| title_full | Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus |
| title_fullStr | Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus |
| title_full_unstemmed | Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus |
| title_short | Reduced Let-7f in Bone Marrow-Derived Mesenchymal Stem Cells Triggers Treg/Th17 Imbalance in Patients With Systemic Lupus Erythematosus |
| title_sort | reduced let 7f in bone marrow derived mesenchymal stem cells triggers treg th17 imbalance in patients with systemic lupus erythematosus |
| topic | let-7f miRNA systemic lupus erythematosus bone marrow derived mesenchymal stem cell interlukin 6 regulatory T cell (Treg) T help cell 17 (Th17) |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00233/full |
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