Liao Fei, Lu Xiaohong, Dong Weiguo
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
IUBMB Life. 2020 Oct 26. doi: 10.1002/iub.2385.
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.
先前的研究已经证明调节性T(Treg)细胞对炎症性肠病(IBD)具有治疗作用,但其机制尚不清楚。外泌体已被认为是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,并探索其潜在机制。从BALB/c小鼠脾脏单核细胞中分离出Treg-Exo,然后将其注射到由葡聚糖硫酸钠(DSS)暴露诱导的IBD小鼠模型中。在存在TNF-α的情况下,使用Treg-Exo与结肠上皮YAMC细胞的共培养模型来研究Tregs与肠上皮细胞之间的通讯。体外实验结果表明,Treg-Exo可以转移到YAMC细胞中,在那里Treg-Exo促进细胞增殖并抑制细胞凋亡。动物实验表明,给予Treg-Exo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在体外和体内的治疗作用均被消除。促凋亡的半胱天冬酶12被确定为miR-195a-3p的直接靶点。总之,Treg-Exo通过转移miR-195a-3p减轻了DSS诱导的IBD。