Tokishakuyakusan, a traditional Japanese medicine (Kampo) mitigates iNKT cell-mediated pregnancy loss in mice
Tokishakuyakusan, a traditional Japanese medicine (Kampo) mitigates iNKT cell-mediated pregnancy loss in mice
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DOI：
10.1111/aji.13021
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发表时间：
2018-10-01
影响因子：
3.6
通讯作者：
Fujii, Tomoyuki
中科院分区：
文献类型：
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作者：
Nagamatsu, Takeshi;Fujii, Tatsuya;Fujii, Tomoyuki
Tokishakuyakusan（TSS）是一种传统的草药，已被经验性地用于预防复发性流产。其行动方式仍不清楚。由于其产生细胞因子的强大能力，恒定自然杀伤（iNKT）细胞参与妊娠早期母胎免疫的控制。本研究旨在澄清TSS对iNKT细胞活性的影响，在一个良好的研究小鼠流产model.Methodspregnant小鼠饲喂1%TSS含或控制饮食从阴道栓形成的一天。在交配后（pc）第9.5天，将α-半乳糖神经酰胺（AGC）腹腔内给予妊娠小鼠，以刺激iNKT细胞。使用细胞因子阵列评估外周细胞因子水平。通过流式细胞术分析检测脾细胞中iNKT细胞的百分比。妊娠丢失的发生率进行了评估，在第12.5天pc。ResultsThe胎儿吸收的总概念的比例显着高于组暴露于TSS（34%）比对照组（78%）。AGC给药后2 h，在对照动物外周血中检测到包括IFN-α和TNF-α在内的炎性细胞因子的快速和强烈的激增。与对照组相比，TSS喂养组的外周细胞因子诱导显著减弱。总脾细胞中的iNKT细胞的百分比是较低的TSS喂养组比在controls.ConclusionThe研究结果表明，TSS对妊娠丢失的抑制作用可能涉及在妊娠早期的iNKT细胞的免疫调节。
ObjectiveTokishakuyakusan (TSS) is a traditional herbal medicine that has been used empirically to prevent recurrent pregnancy loss. Its mode of action remains unclear. With their potent capacity to produce cytokines, invariant natural killer (iNKT) cells are involved in the control of fetomaternal immunity in early gestation. This study aimed to clarify the effect of TSS on iNKT cell activities in a well-studied murine miscarriage model.MethodsPregnant mice were fed 1% TSS-containing or control diet from the day of vaginal plug formation. Alpha-galactosylceramide (AGC) was administered intraperitoneally to the pregnant mice at day 9.5 postcoitus (pc) to stimulate iNKT cells. Peripheral cytokine levels were evaluated using cytokine arrays. The percentage of iNKT cells among splenocytes was examined by flow cytometric analysis. The incidence of pregnancy loss was assessed at day 12.5 pc.ResultsThe ratio of fetal resorptions to total conceptuses was significantly higher in the group exposed to TSS (34%) than in controls (78%). A rapid and robust surge in inflammatory cytokines, including IFN- and TNF-, was detected in the peripheral blood of control animals 2hours after AGC administration. This peripheral cytokine induction was significantly attenuated in the TSS-fed group compared with the control. The percentage of iNKT cells among total splenocytes was lower in the TSS-fed group than in controls.ConclusionThe findings in this study suggest that the inhibitory effects of TSS on pregnancy loss may involve immune modulation of iNKT cells during early pregnancy.