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人牙龈间充质干细胞通过依赖于 IL-10 信号的免疫细胞调节缓解炎症性肠病。

Human gingiva-derived mesenchymal stem cells alleviate inflammatory bowel disease via IL-10 signalling-dependent modulation of immune cells.

机构信息

Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Scand J Immunol. 2019 Sep;90(3):e12751. doi: 10.1111/sji.12751. Epub 2019 Jul 8.

Abstract

Current evidence indicates that inflammatory bowel disease (IBD) is caused primarily by impaired mucosal immunity, resulting in an imbalance between epithelial barrier function and tissue inflammation. Human gingiva-derived mesenchymal stem cells (GMSCs) exhibit immunomodulatory and anti-inflammatory effects in a variety of immunity- and inflammation-associated diseases. However, the role of GMSCs in treating IBD has not been elucidated. Our study, therefore, examined the therapeutic effect and mechanism of GMSCs in a murine colitis model of IBD. Our results indicate that the infusion of GMSCs significantly prolonged survival and relieved symptoms. Phenotype analyses showed that the frequencies of NK1.1 and CD11b cells, as well as CD4 T cells in the spleen, were suppressed in GMSC-treated mice compared with the PBS- or fibroblast-treated control groups. Additionally, GMSC treatment markedly increased the numbers of interleukin (IL)-10 regulatory T cells, reduced the secretion of pro-inflammatory cytokines, and increased production of anti-inflammatory cytokines. A mechanistic study revealed that anti-IL-10R antibody abolished the protective effect of GMSCs compared with mice treated with anti-IgG antibody. Thus, our results indicate that GMSCs play a critical role in alleviating colitis by modulating inflammatory immune cells via IL-10 signalling.

摘要

目前的证据表明,炎症性肠病(IBD)主要是由黏膜免疫受损引起的,导致上皮屏障功能和组织炎症之间失衡。人牙龈来源的间充质干细胞(GMSCs)在多种免疫和炎症相关疾病中具有免疫调节和抗炎作用。然而,GMSCs 在治疗 IBD 中的作用尚未阐明。因此,我们研究了 GMSCs 在 IBD 小鼠结肠炎模型中的治疗作用和机制。我们的结果表明,GMSCs 的输注显著延长了存活时间并缓解了症状。表型分析表明,与 PBS 或成纤维细胞处理的对照组相比,GMSC 处理小鼠脾中 NK1.1 和 CD11b 细胞以及 CD4 T 细胞的频率受到抑制。此外,GMSC 治疗显著增加了白细胞介素(IL)-10 调节性 T 细胞的数量,减少了促炎细胞因子的分泌,并增加了抗炎细胞因子的产生。机制研究表明,与用抗 IgG 抗体处理的小鼠相比,抗 IL-10R 抗体消除了 GMSCs 的保护作用。因此,我们的结果表明,GMSCs 通过 IL-10 信号通路调节炎症免疫细胞在缓解结肠炎中发挥关键作用。

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