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瘦素作为一种促炎细胞因子,与肿瘤的免疫逃逸机制有关,但其在妊娠期母体免疫应答中的作用尚不明了。为了探讨瘦素在促进胎盘滋养细胞Ib类组织相容性抗原HLA-G表达中的作用机制,揭示妊娠期母体免疫应答可能的调节方式,本研究通过分离胎盘CTB和EVT、采集胎盘外植体和培养细胞后,用寡聚脱氧核苷酸抑制瘦素表达,采用qRT-PCR、Western blotting和免疫荧光检测了HLA-G表达情况。研究发现,滋养细胞来源的JEG-3细胞系与25～50 ng/mL的重组瘦素进行体外孵育后显著促进了HLA-G mRNA和蛋白的表达,并且在抑制PI3K-Akt信号通路后,HLA-G表达显著降低,且在足月胎盘组织外植体中观察到类似的瘦素刺激作用;此外,用瘦素反义寡聚脱氧核苷酸处理的JEG-3细胞表现较低的HLA-G表达水平;免疫荧光和q PCR分析证实了胎盘组织中瘦素的生物合成,进一步表明侵袭性绒毛外滋养层细胞在正常妊娠的前三个月期间是瘦素的主要来源。本研究表明,瘦素作为促进胎盘滋养细胞中HLA-G表达的自分泌/旁分泌信号,在母胎界面上调节免疫逃避机制中起重要作用。
Abstract：Leptin, a proinflammatory cytokine, is involved in the immune escape mechanism of tumors, but its role in maternal immune response during pregnancy is unclear. To investigate the mechanism of leptin in promoting the expression of HLA-G of placental trophoblast Class Ib histocompatibility antigen and to reveal the possible regulation of maternal immune response during pregnancy, In this study, we separated placental CTB and EVT, collected of placental explants and culture cells, and inhibited leptin's expression by oligonucleotide, the expression of HLA-G was detected by qRT-PCR, Western blotting and immunofluorescence. JEG-3 cells derived from trophoblast cells and recombinant leptin(25～50 ng/mL) could significantly promote the expression of HLA-G mRNA and protein after in vitro incubation, and after inhibit the PI3 K-Akt signaling pathway, HLA-G expression was significantly reduced, and similar leptin stimulation was observed in full-term placental explants. In addition,JEG-3 cells treated with leptin antisense oligodeoxynucleotides showed lower HLA-G expression levels.Immunofluorescence and qPCR analysis confirmed the biosynthesis of leptin in placental tissue, further demonstrating that aggressive extravillous trophoblast cells are the main source of leptin during the first trimester of normal pregnancy. Leptin, an autocrine/paracrine signal that promotes HLA-G expression in placental trophoblasts, plays an important role in the regulation of immune evasion at the maternal-fetal interface.
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基本信息:
DOI：10.13417/j.gab.038.003836
中图分类号:R392
引用信息:
[1]赵霞.瘦素能促进胎盘滋养细胞HLA-G表达[J].基因组学与应用生物学,2019,38(08):3836-3842.DOI:10.13417/j.gab.038.003836.
2019-08-25
2019-08-25