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Mesenchymal stem cells moderate experimental autoimmune uveitis by dynamic regulating Th17 and Breg cells response

机译:间充质干细胞通过动态调节Th17和Breg细胞反应来缓和实验性自身免疫性葡萄膜炎

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Abstract Mesenchymal stem cells (MSCs) are adult stem cells from mesoderm with multi potential differentiation, and are being widely studied as a promising treatment for autoimmune diseases. The main inflammatory factors of experimental autoimmune uveitis (EAU) are T helper type 1 (Th1) and Th17. Regulatory B cells (Bregs) are a newly designated B cell subgroup, which has been proved to play a key role in regulating inflammation, autoimmunity and cancer. In this regard, we establish the EAU model by injecting interphotoreceptor retinoid‐binding protein combined with complete Freund's adjuvant into the tail vein and bilateral thighs of rats, and inject MSCs or equal volume of phosphate buffer saline intraperitoneally on the day of immunization. Dynamic changes of cell subsets and cytokine expression are tested at different time periods to explore the relationship between MSCs treatment and disease prognosis during EAU course. Our results suggest that compared with the model control group, MSCs treatment can significantly reduce the production of Th1 and Th17 cytokines during EAU, while the production of regulatory B cells (Bregs) cytokines is significantly increased. At the same time, MSCs can reduce the proportion of Th17 in lymphocytes while the proportion of Bregs is elevated, thus inhibiting the differentiation and activity of interleukin in EAU rats. All this results provide more powerful evidence for cell therapy of autoimmune uveitis.
机译:摘要 间充质干细胞(MSCs)是来自中胚层的多潜能分化的成体干细胞,作为一种治疗自身免疫性疾病的药物,被广泛研究。实验性自身免疫性葡萄膜炎 (EAU) 的主要炎症因子是 1 型辅助性 T 细胞 (Th1) 和 Th17。 调节性 B 细胞 (Bregs) 是新指定的 B 细胞亚群,已被证明在调节炎症、自身免疫和癌症中起关键作用。在这方面,我们通过将光感受器间类视黄醇结合蛋白结合完全弗氏佐剂注射到大鼠尾静脉和双侧大腿中来建立EAU模型,并在免疫当天腹膜内注射MSCs或等体积的磷酸盐缓冲盐水。测试不同时间段细胞亚群和细胞因子表达的动态变化,探讨 EAU 病程中间充质干细胞治疗与疾病预后的关系。结果表明,与模型对照组相比,MSCs处理可显著降低EAU期间Th1和Th17细胞因子的产生,而调节性B细胞(Bregs)细胞因子的产生显著增加。同时,间充质干细胞可以降低淋巴细胞中Th17的比例,而Bregs的比例升高,从而抑制EAU大鼠白细胞介素的分化和活性。所有这些结果为自身免疫性葡萄膜炎的细胞治疗提供了更有力的证据。

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