PMID- 33238163 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20220107 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 229 DP - 2021 Jan TI - Combining miR-23b exposure with mesenchymal stem cell transplantation enhances therapeutic effects on EAE. PG - 18-26 LID - S0165-2478(20)30418-1 [pii] LID - 10.1016/j.imlet.2020.11.007 [doi] AB - Bone marrow mesenchymal stem cells (BMSCs) have the immuno-modulatory capacity to ameliorate autoimmune diseases, such as multiple schlerosis (MS), systemic lupus erythematosus and rheumatoid arthritis. However, BMSC-mediated immunosuppression can be challenging to achieve. The efficacy of BMSC transplantation may be augmented by an adjuvant therapy. Here, we demonstrated that treatment of mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, with BMSCs over-expressing microRNA (miR)-23b provided better synergistic and longer-term therapeutic effects than treatment with traditional BMSCs. Over-expression of miR-23b enhanced the ability of BMSCs to inhibit differentiation of Th17 cells and reduced IL-17 secretion. Compared to traditional BMSCs, the miR-23b over-expressing BMSCs (miR23b-BMSCs) exhibited enhanced secretion of tumor growth factor beta 1 (TGF-beta(1)), a cytokine that promotes the differentiation of regulatory T (Treg) cells. Pathologically, miR23b-BMSC transplantation delayed EAE progression, apparently by reducing the Th17/Treg cell ratio and inhibiting inflammatory cell infiltration across the blood-brain barrier, and thus slowing spinal cord demyelination. These results may lead to better utility of BMSCs as a treatment for autoimmune diseases. CI - Copyright (c) 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - Hu, Ruixue AU - Hu R AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Lv, Weiqi AU - Lv W AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Zhang, Sifan AU - Zhang S AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Liu, Yumei AU - Liu Y AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Sun, Bo AU - Sun B AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Meng, Yanting AU - Meng Y AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Kong, Qingfei AU - Kong Q AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Mu, Lili AU - Mu L AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Wang, Guangyou AU - Wang G AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Zhang, Yao AU - Zhang Y AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Li, Hulun AU - Li H AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. FAU - Liu, Xijun AU - Liu X AD - Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. Electronic address: lxj@hrbmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201122 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (MicroRNAs) RN - 0 (Mirn23b microRNA, mouse) SB - IM MH - Animals MH - Biomarkers MH - Cell Line MH - Cytokines/metabolism MH - Disease Management MH - Disease Models, Animal MH - Disease Susceptibility MH - Encephalomyelitis, Autoimmune, Experimental/diagnosis/*etiology/*therapy MH - Gene Expression MH - Genetic Vectors/genetics MH - Humans MH - Immunophenotyping MH - Inflammation Mediators/metabolism MH - *Mesenchymal Stem Cell Transplantation/methods MH - Mesenchymal Stem Cells/*cytology/*metabolism MH - Mice MH - MicroRNAs/*genetics MH - Signal Transduction MH - Spinal Cord/immunology/metabolism/pathology MH - T-Lymphocytes/immunology/metabolism MH - Transduction, Genetic MH - Treatment Outcome OTO - NOTNLM OT - Bone mesenchymal stem cells OT - Experimental autoimmune encephalomyelitis OT - Lentivirus packaging system OT - MiR-23b OT - Multiple sclerosis EDAT- 2020/11/26 06:00 MHDA- 2022/01/08 06:00 CRDT- 2020/11/25 20:05 PHST- 2020/09/02 00:00 [received] PHST- 2020/11/01 00:00 [revised] PHST- 2020/11/18 00:00 [accepted] PHST- 2020/11/26 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2020/11/25 20:05 [entrez] AID - S0165-2478(20)30418-1 [pii] AID - 10.1016/j.imlet.2020.11.007 [doi] PST - ppublish SO - Immunol Lett. 2021 Jan;229:18-26. doi: 10.1016/j.imlet.2020.11.007. Epub 2020 Nov 22.