1 Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.
2 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Reprod Sci. 2019 Apr;26(4):532-542. doi: 10.1177/1933719118777638. Epub 2018 Jun 18.
Decidual γδ T cells are known to regulate the function of trophoblasts at the maternal-fetal interface; however, little is known about the molecular mechanisms of cross talk between trophoblast cells and decidual γδ T cells.
Expression of chemokine C-X-C motif ligand 6 (CXCL16) and its receptor CXCR6 was evaluated in first-trimester human villus and decidual tissues by immunohistochemistry. γδ T cells were isolated from first-trimester human deciduae and cocultured with JEG3 trophoblast cells. Cell proliferation and apoptosis-related molecules, together with cytotoxicity factor and cytokine production, were measured by flow cytometry analysis.
Expression of CXCL16 and CXCR6 was reduced at the maternal-fetal interface in patients who experienced unexplained recurrent spontaneous abortion as compared to healthy pregnancy women. With the administration of pregnancy-related hormones or coculture with JEG3 cells, CXCR6 expression was upregulated on decidual γδ T cells. CXCL16 derived from JEG3 cells caused a decrease in granzyme B production of decidual γδ T cells. In addition, decidual γδ T cells educated by JEG3-derived CXCL16 upregulated the expression of Bcl-xL in JEG3 cells.
This study suggested that the CXCL16/CXCR6 axis may contribute to maintaining normal pregnancy by reducing the secretion of cytotoxic factor granzyme B of decidual γδ T cells and promoting the expression of antiapoptotic marker Bcl-xL of trophoblasts.
已知蜕膜 γδ T 细胞可调节母胎界面滋养层细胞的功能；然而，滋养层细胞与蜕膜 γδ T 细胞之间的串扰的分子机制知之甚少。
通过免疫组织化学法评估人早孕绒毛和蜕膜组织中趋化因子 C-X-C 基元配体 6（CXCL16）及其受体 CXCR6 的表达。从早孕蜕膜中分离出 γδ T 细胞并与 JEG3 滋养层细胞共培养。通过流式细胞术分析检测细胞增殖和凋亡相关分子以及细胞毒性因子和细胞因子的产生。
与健康妊娠妇女相比，经历不明原因复发性自然流产的患者其母胎界面处 CXCL16 和 CXCR6 的表达减少。给予妊娠相关激素或与 JEG3 细胞共培养后，蜕膜 γδ T 细胞上 CXCR6 的表达上调。来自 JEG3 细胞的 CXCL16 导致蜕膜 γδ T 细胞中颗粒酶 B 的产生减少。此外，JEG3 衍生的 CXCL16 诱导的蜕膜 γδ T 细胞上调 JEG3 细胞中抗凋亡标志物 Bcl-xL 的表达。
本研究表明，CXCL16/CXCR6 轴可能通过减少蜕膜 γδ T 细胞中细胞毒性因子颗粒酶 B 的分泌并促进滋养层细胞抗凋亡标志物 Bcl-xL 的表达，从而有助于维持正常妊娠。
