绒毛外泌体递送HLA-G增强人蜕膜NK细胞表达骨诱导因子(OGN)和多效生长因子(PTN)  

Villi exosomes deliver HLA-G to enhance the expression of osteoglycin and pleiotrophin in decidual NK cells

作　　者：方正 茅佳钦 陈书强 董杰 王晓红 FANG Zheng;MAO Jiaqin;CHEN Shuqiang;DONG Jie;WANG Xiaohong(Reproductive Medicine Center,Department of Obstetrics and Gynecology,Tangdu Hospital,Air Force Medical University,Xi’an 710038,China)

机构地区：[1]空军军医大学唐都医院妇产科生殖医学中心,陕西西安710038

出　　处：《细胞与分子免疫学杂志》2022年第6期535-541,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81871182)。

摘　　要：目的探究人绒毛组织来源含人类白细胞抗原G(HLA⁃G)外泌体对蜕膜自然杀伤(dNK)细胞分泌骨诱导因子(OGN)和多效生长因子(PTN)功能的影响。方法将不明原因复发性流产患者与正常人工流产患者绒毛组织来源含HLA⁃G外泌体与dNK细胞共培养,实时定量PCR和Western blot法分别检测dNK细胞OGN和PTN的mRNA和蛋白表达。通过慢病毒LV⁃HLA⁃G感染HTR⁃8/Svneo人绒毛滋养细胞细胞系,得到过表达HLA⁃G外泌体(HLA⁃G^(OE)⁃EXO)。将HLA⁃G^(OE)⁃EXO与dNK细胞共培养,采用以上方法检测OGN与PTN表达。将HLA⁃G^(OE)⁃EXO与dNK细胞培养后上清与HTR⁃8/Svneo共培养,CCK⁃8法检测HTR⁃8/Svneo细胞的增殖情况。结果正常人工流产患者绒毛组织来源外泌体较复发性流产组患者可显著增强dNK细胞OGN与PTN表达。HLA⁃G^(OE)⁃EXO可显著增强dNK细胞OGN与PTN表达,其上清可促进HTR⁃8/Svneo细胞增殖。结论人母胎界面绒毛组织可通过产生含HLA⁃G外泌体影响dNK细胞功能,促进其分泌促生长因子。Objective To identify the effect of HLA⁃G⁃containing exosomes on the secretory function of growth⁃promoting factors osteoglycin(OGN)and pleiotrophin(PTN)by decidual NK(dNK)cells.Methods dNK cells were co⁃cultured with HLA⁃G⁃containing exosomes from the villi of patients undergoing unexplained recurrent pregnancy loss(uRPL)and normal induced abortion,respectively.Sequentially,OGN and PTN of the dNK cells were determined using real time quantitative PCR and western blotting.Exosomes overexpressing HLA⁃G(HLA⁃G^(OE)⁃EXO)were obtained by transfecting the villous trophoblast cell line HTR⁃8/Svneo with lentivirus LV⁃HLA⁃G.dNK cells were further co⁃cultured with HLA⁃G^(OE)⁃EXO for detecting the expression of OGN and PTN,the culture supernatant of which was used to treat HTR⁃8/Svneo cells,and the proliferation of HTR⁃8/Svneo cells was detected by the CCK⁃8 assay.Results Exosomes derived from villi of patients receiving normal induced abortion significantly enhanced the expression of OGN and PTN in dNK cells compared with those from patients of the uRPL group.Besides,HLA⁃G^(OE)⁃EXO markedly enhanced the expression of OGN and PTN in dNK cells.The culture supernatant of HLA⁃G^(OE)⁃EXO treated dNK cells could promote the proliferation of HTR⁃8/Svneo cells.Conclusion Villi⁃derived HLA⁃G containing exosomes may enhance the secretion of growth⁃promoting factors in dNK cells.

关 键 词：蜕膜自然杀伤(dNK)细胞 外泌体 人类白细胞分化抗原G(HLA-G) 骨诱导因子(OGN) 多效生长因子(PTN) 

分 类 号：R714.21[医药卫生—妇产科学] R392.9[医药卫生—临床医学] R392-33