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Exosomes derived from T regulatory cells relieve inflammatory bowel disease by transferring miR ‐195a‐3p
IUBMB Life ( IF 3.7 ) Pub Date : 2020-10-26 , DOI: 10.1002/iub.2385
Fei Liao 1 , Xiaohong Lu 1 , Weiguo Dong 1
Affiliation  

Previous studies have demonstrated the therapeutic effects of regulatory T (Treg) cells on inflammatory bowel disease (IBD), but the mechanism is not well‐understood. Exosomes have been proposed as a novel mechanism underlying the action of Tregs. This study aimed to investigate the therapeutic effects of exosomes secreted by Treg cells (Treg‐Exo) on IBD and to explore the underlying mechanism. Treg‐Exo was isolated from BALB/c mouse spleen mononuclear cells and then injected into a murine model of IBD induced by dextran sodium sulfate (DSS) exposure. A co‐culture model of Treg‐Exo and colonic epithelial YAMC cells in the presence of TNF‐α was used to investigate the communication between Tregs and intestinal epithelial cells. in vitro results showed that Treg‐Exo could be transferred to YAMC cells where Treg‐Exo promoted cell proliferation and inhibited cell apoptosis. Animal experiments showed that Treg‐Exo administration alleviated the DSS‐induced IBD in mice. The therapeutic effects of Treg‐Exo both in vitro and in vivo were eliminated when miR‐195a‐3p expression was inhibited in Treg‐Exo. The pro‐apoptotic Caspase 12 was identified as a direct target of miR‐195a‐3p. In conclusion, Treg‐Exo alleviated the DSS‐induced IBD through transferring miR‐195a‐3p.

中文翻译:


T 调节细胞衍生的外泌体通过转移 miR ‐195a-3p 缓解炎症性肠病



先前的研究已经证明调节性T(Treg)细胞对炎症性肠病(IBD)有治疗作用,但其机制尚不清楚。外泌体被认为是 Tregs 作用的一种新机制。本研究旨在探讨Treg细胞分泌的外泌体(Treg-Exo)对IBD的治疗作用并探讨其潜在机制。 Treg-Exo 从 BALB/c 小鼠脾单核细胞中分离出来,然后注射到由葡聚糖硫酸钠 (DSS) 暴露诱导的 IBD 小鼠模型中。在 TNF-α 存在下,使用 Treg-Exo 和结肠上皮 YAMC 细胞的共培养模型来研究 Tregs 和肠上皮细胞之间的通讯。体外结果表明,Treg-Exo可以转移到YAMC细胞中,其中Treg-Exo促进细胞增殖并抑制细胞凋亡。动物实验表明,Treg-Exo 给药可减轻 DSS 诱导的小鼠 IBD。当 Treg-Exo 中的 miR-195a-3p 表达受到抑制时,Treg-Exo 的体外和体内治疗作用均被消除。促凋亡 Caspase 12 被确定为 miR-195a-3p 的直接靶标。总之,Treg-Exo 通过转移 miR-195a-3p 减轻了 DSS 诱导的 IBD。
更新日期:2020-10-26
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