Dual expression of CXCR4 and IL-35 enhances the therapeutic effects of BMSCs on TNBS-induced colitis in rats through expansion of Tregs and suppression of Th17 cells
Dual expression of CXCR4 and IL-35 enhances the therapeutic effects of BMSCs on TNBS-induced colitis in rats through expansion of Tregs and suppression of Th17 cells
复制标题
CXCR4 和 IL-35 的双重表达通过扩增 Tregs 和抑制 Th17 细胞增强 BMSC 对 TNBS 诱导的大鼠结肠炎的治疗作用
DOI：
10.1016/j.bbrc.2018.03.043
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发表时间：
2018-05-23
影响因子：
3.1
通讯作者：
Deng, Shuangjiao
中科院分区：
文献类型：
--
作者：
Nan, Zhen;Fan, Heng;Deng, Shuangjiao
骨髓间充质干细胞（BMSCs）由于其免疫抑制特性和组织愈合潜力，在炎症性肠病的治疗中具有很大的前景。调节性T细胞（Tcells）和辅助性T细胞（Th）17之间的平衡在BMSC介导的免疫抑制中起着至关重要的作用。白细胞介素（IL）-35是一种新发现的抗炎细胞因子，用于扩增Treg和抑制Th 17细胞分化。当IL-35在这些细胞中过表达时，IL-35可以增强BMSC的免疫抑制特性。然而，骨髓间充质干细胞在体内的修复能力是有限的，部分原因是骨髓间充质干细胞对炎症结肠的归巢效率差。BMSCs中CXC趋化因子受体4（CXCR 4）表达上调可能通过基质衍生因子-1影响植入BMSCs的定向归巢。本研究通过慢病毒介导的CXCR 4和IL-35基因修饰大鼠BMSCs，观察到基因工程BMSCs迁移能力增强，免疫调节活性增强。这些结果表明，通过CXCR 4和IL-35的双重表达修饰BMSCs可能为炎症性肠病提供有效的治疗策略。(C)2018爱思唯尔公司All rights reserved.
Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for the treatment of inflammatory bowel disease owing to their immunosuppressive property and tissue healing potential. The balance between regulatory T cells (Tregs) and T helper (Th)17 cells plays a crucial role in BMSC-mediated immunosuppression. Interleukin (IL)-35 is a newly identified anti-inflammatory cytokine required for the expansion of Tregs and suppression of Th17 cell differentiation. IL-35 can amplify the immunosuppressive property of BMSCs when overexpressed in these cells. However, the reparative capability of BMSCs in vivo is limited, partly due to the poor homing efficiency of BMSCs to inflamed colons. Up-regulation of CXC chemokine receptor 4 (CXCR4) expression in BMSCs may affect the directional homing of implanted BMSCs via stromal-derived factor-1. In this study, by lentivirus-mediated introduction of CXCR4 and IL-35 genes to modify rat BMSCs, we observed enhanced migration and strengthened immunomodulatory activities of the genetically engineering BMSCs. These results suggest that modification of BMSCs by dual expression of CXCR4 and IL-35 may provide an effective therapeutic strategy for inflammatory bowel disease. (C) 2018 Elsevier Inc. All rights reserved.