实用医学杂志 ›› 2022, Vol. 38 ›› Issue (1): 26-37.doi: 10.3969/j.issn.1006⁃5725.2022.01.006

• 基础研究 • 上一篇    下一篇

过表达IDO不同分子轴调节骨髓间充质干细胞分泌外泌体通过DC及T细胞

刘星佑1 陈鑫昊2 黄尹霞2 李敏2 撒亚莲2 贺继刚2   

  1. 1 云南中医药大学(昆明 650000);2 云南省第一人民医院心脏大血管外科(昆明 650000)

  • 出版日期:2022-01-10 发布日期:2022-01-10
  • 通讯作者: 贺继刚 E⁃mail:jiganghe999@163.com
  • 基金资助:
    国家自然科学基金(编号:82060299);云南省专业学位研究生教学案例库建设项目(编号:YJS⁃SJ⁃02);云南省卫生健康委员会医学学科带头人培养计划(编号:D⁃2019020);云南省政府万人计划⁃青年拔尖人才(编号:KH⁃SWR⁃QNBJ⁃2019⁃002);云南省科技厅⁃昆明医科大学应用基础研究联合专项(编号:202101AY070001⁃034;2019FE001(⁃120));云南省第一人民医院临床医学中心开放项目(编号:2021LCZXXF⁃XZ04);昆医联合专项杰出青年培育项目(编号:202101AY070001⁃034)

Exosome secreted by bone marrow mesenchymal stem cells overexpressing IDO regulating DC and T Cells through different molecular axes

LIU Xingyou*,CHEN Xinhao,HUANG Yinxia,LI Min,SA Yalian,HE Jigang.   

  1. Yunnan University of Chinese Medicine,Kunming 650000,China

  • Online:2022-01-10 Published:2022-01-10
  • Contact: HE Jigang E⁃mail:jiganghe999@163.com

摘要:

目的 探讨过表达吲哚胺 2,3 双加氧酶(IDO)间充质干细胞分泌外泌体(BMSCIDO⁃exosome 抑制T及DC细胞激活机制。方法 将BMSCIDO⁃exosome与DC、T细胞共培养设立为实验组。检测共培养DC T 细胞内 miR⁃540⁃3p、CD74、CD28、CCL4、p⁃ERK1/2、p⁃NF⁃κB、p⁃AKT表达。验证miRNA⁃540⁃3p与CD74 因的靶向结合。结果 实验组中 DC 细胞内 miR⁃540⁃3p 表达增高,CD74、p⁃p65 表达降低。T细胞内miR⁃ 540⁃3p表达增高,CD74、p⁃AKT表达降低。miRNA⁃540⁃3pCD74 可以靶向结合。结论 BMSCIDO⁃exosome 通过 miRNA⁃540⁃3p(+)/CD74(-)/p⁃NF⁃κB 分子轴抑制 DC 细胞的激活。通过miRNA⁃540⁃3p(+)/CD74(-)/ p⁃AKT(-)分子轴抑制T细胞的激活。

关键词:

吲哚胺2, 3双加氧酶, 外泌体, miRNA?540?3p, 免疫抑制

Abstract:

Objective This study aimed to explore the mechanism of exosome secreted by bone mesenchy⁃ mal stem cells overexpressing IDO(BMSCIDO⁃exosome)inhibiting the activation of T and DC cells. Method The experimental group consisted of BMSCIDO⁃exosome was co⁃cultured with DC and T cells. In co⁃cultured DC and T cells,the expression of miR⁃540⁃3p,CD74,CD28,CCL4,p⁃ERK1/2,p⁃NF⁃κB,and p⁃AKT was detected. The targeted binding of miRNA⁃540⁃3p to CD74 gene was also verified. Results In the experimental group,miR⁃540⁃ 3p expression increased in DC cells while CD74 and p⁃p65 expression decreased. MiR⁃540⁃3p expression increased in T cells,while CD74 and p⁃AKT expression decreased. MiRNA⁃540⁃3p has been shown to bind specifically to CD74. Conclusions BMSCIDO⁃exosome could inhibit the activation of DC and T cells through the miRNA⁃540⁃3p (+)/CD74(-)/p⁃NF⁃κB molecular axis and the miRNA⁃540⁃3p(+)/CD74(-)/p⁃AKT(-)molecular axis,respec⁃ tively.

Key words:

indoleamine 2, 3 dioxygenase, exosome, miRNA?540?3p, immunologic suppression