Human gingiva-derived mesenchymal stem cells alleviate inflammatory bowel disease via IL-10 signalling-dependent modulation of immune cells
Human gingiva-derived mesenchymal stem cells alleviate inflammatory bowel disease via IL-10 signalling-dependent modulation of immune cells
复制标题
人牙龈源性间充质干细胞通过 IL-10 信号依赖性免疫细胞调节减轻炎症性肠病
DOI：
10.1111/sji.12751
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发表时间：
2019
影响因子：
3.7
通讯作者：
Gu Jian
中科院分区：
文献类型：
--
作者：
Lu Yousheng;Xu Yueran;Zhang Shaopeng;Gao Ji;Gan Xiaojie;Zheng Ju;Lu Ling;Zeng Wenquan;Gu Jian
目前的证据表明，炎症性肠病(IBD)主要是由于黏膜免疫受损，导致上皮屏障功能和组织炎症之间的失衡。人牙龈间充质干细胞(GMSCs)在多种免疫和炎症相关疾病中表现出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，我们的研究考察了GMSCs在IBD小鼠结肠炎模型中的治疗效果和机制。我们的结果表明，GMSCs的输注显着延长了存活期，缓解了症状。表型分析显示，与PBS或成纤维细胞处理的对照组相比，GMSC处理的小鼠脾中NK1.1+和CD11b+细胞以及CD4T细胞的频率受到抑制。此外，GMSC治疗可显著增加IL-10+调节性T细胞的数量，减少促炎细胞因子的分泌，增加抗炎细胞因子的产生。一项机制研究表明，与抗Ig G抗体处理的小鼠相比，抗IL-10R抗体取消了GMSCs的保护作用。因此，我们的结果表明，GMSCs通过IL-10信号调节炎症免疫细胞，从而在缓解结肠炎方面发挥关键作用。
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.