Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Am J Reprod Immunol. 2023 Jun;89(6):e13581. doi: 10.1111/aji.13581. Epub 2022 Jul 1.
Recurrent pregnancy loss (RPL) is a common disease characterized by immune dysfunction and vitamin D deficiency. This study aimed to investigate vitamin D metabolism and γδT cell phenotypes at the maternal-fetal interface in women with early normal pregnancy (NP) and RPL and to determine the effects of vitamin D on the functions of γδT cells and their crosstalk with trophoblasts.
The levels of 25-(OH)VD , the expression of vitamin D metabolic enzymes in the villi, and the proportion of γδT cells in the decidua were detected in women with NP and RPL. After treatment with different concentrations of vitamin D, the mRNA expression of the vitamin D receptor (VDR), cytokines, and transcription factors were detected in Vδ2 γδT cells. In addition, the proliferation, migration, and invasion of HTR-8/SVneo trophoblasts were determined by coculturing them with vitamin D-treated Vδ2 γδT cells and their supernatants.
In women with RPL, the level of 25-(OH)VD in the villi was increased; however, that of CYP27B1 (enzyme converting 25-(OH)VD into 1,25-(OH) VD ) was decreased. In addition, the proportion of Vδ2 γδT cells increased, whereas that of Foxp3 Vδ2 γδT cells decreased in the decidua of women with RPL. An in vitro study showed that vitamin D increased the expression of VDR mRNA and Foxp3, but decreased the expression of IFN-γ mRNA, in Vδ2 γδT cells. Finally, vitamin D-treated Vδ2 γδT cells promoted trophoblast migration and invasion.
Abnormal vitamin D metabolism and γδT cell proportions were present at the maternal-fetal interface in women with RPL. Under normal pregnancy conditions, vitamin D can induce the differentiation of decidual Vδ2 γδT cells toward an anti-inflammatory phenotype (Treg-like γδT cells) and modulate the crosstalk between Vδ2 γδT cells and trophoblasts.
复发性流产（RPL）是一种常见疾病，其特征为免疫功能障碍和维生素 D 缺乏。本研究旨在探讨早孕期正常妊娠（NP）和 RPL 患者母胎界面的维生素 D 代谢和 γδT 细胞表型，并确定维生素 D 对 γδT 细胞功能及其与滋养层细胞相互作用的影响。
检测 NP 和 RPL 患者绒毛 25-（OH）VD 水平、维生素 D 代谢酶的表达以及蜕膜中 γδT 细胞的比例。用不同浓度的维生素 D 处理 Vδ2 γδT 细胞后，检测维生素 D 受体（VDR）、细胞因子和转录因子的 mRNA 表达。此外，通过与经维生素 D 处理的 Vδ2 γδT 细胞及其上清液共培养，测定 HTR-8/SVneo 滋养层细胞的增殖、迁移和侵袭。
RPL 患者绒毛中 25-（OH）VD 水平升高，而 CYP27B1（将 25-（OH）VD 转化为 1,25-（OH）VD 的酶）水平降低。此外，RPL 患者蜕膜中 Vδ2 γδT 细胞比例增加，而 Foxp3 Vδ2 γδT 细胞比例降低。体外研究表明，维生素 D 增加了 Vδ2 γδT 细胞中 VDR mRNA 和 Foxp3 的表达，降低了 IFN-γ mRNA 的表达。最后，经维生素 D 处理的 Vδ2 γδT 细胞促进了滋养层细胞的迁移和侵袭。
RPL 患者母胎界面存在异常的维生素 D 代谢和 γδT 细胞比例。在正常妊娠情况下，维生素 D 可诱导蜕膜中 Vδ2 γδT 细胞向抗炎表型（Treg 样 γδT 细胞）分化，并调节 Vδ2 γδT 细胞与滋养层细胞之间的相互作用。
