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不变自然杀伤T细胞通过涉及Th1和Th17反应的机制增加脂多糖诱导的妊娠丢失。

Invariant NKT cells increase lipopolysacchride-induced pregnancy loss by a mechanism involving Th1 and Th17 responses.

作者信息

Li Liping, Yang Jing, Ren Lihua, Su Ning, Fang Yichuan, Lin Yi

机构信息

Department of Obstetrics and Gynecology, Guangzhou Medical College Affiliated Guangzhou First People's Hospital, Guangzhou, China.

出版信息

J Matern Fetal Neonatal Med. 2013 Aug;26(12):1212-8. doi: 10.3109/14767058.2013.773307. Epub 2013 Mar 6.

DOI:10.3109/14767058.2013.773307
PMID:23406501
Abstract

OBJECTIVE

To determine the role of invariant natural killer T (iNKT) cells in infection-associated pregnancy loss.

METHODS

B6 and iNKT cell-deficient Jα18(-/-) mice were injected i.p. with lipopolysaccharide (LPS) or vehicle, and pregnancy outcomes were examined. Decidual iNKT cell expression of CD69 and intracellular cytokine production were analyzed. Mouse decidual iNKT cells were co-cultured with LPS or PBS-treated dendritic cells (DCs), and iNKT cell CD69 expression and intracellular and extracellular cytokine production were assessed.

RESULTS

The embryo resorption rate was notably lessened for Jα18(-/-) mice treated with LPS on day 6 or day 9 gestation in comparison with B6 mice treated with LPS. Decidual iNKT cell CD69 expression and intracellular IFN-γ and IL-17 production for B6 mice injected with LPS on day 6 or day 9 gestation were significantly up-regulated compared with PBS-treated mice. Levels of IFN-γ and IL-17 in the supernatants of the co-culture of decidual iNKT cells and LPS-sensitized DCs were strikingly increased in comparison with the co-culture of iNKT cells and PBS-treated DCs. CD69 expression and intracellular IFN-γ and IL-17 production of iNKT cells co-cultured with LPS-sensitized DCs were remarkably up-regulated compared with iNKT cells co-cultured with PBS-treated DCs.

CONCLUSIONS

Our results suggest that iNKT cells may play a role in LPS-induced pregnancy loss by Th1 and Th17 cytokine-dependent manner.

摘要

目的

确定不变自然杀伤T(iNKT)细胞在感染相关的妊娠丢失中的作用。

方法

给B6小鼠和iNKT细胞缺陷的Jα18(-/-)小鼠腹腔注射脂多糖(LPS)或赋形剂,然后检查妊娠结局。分析蜕膜中iNKT细胞CD69的表达及细胞内细胞因子的产生情况。将小鼠蜕膜iNKT细胞与经LPS或PBS处理的树突状细胞(DCs)共培养,评估iNKT细胞CD69的表达以及细胞内和细胞外细胞因子的产生情况。

结果

与接受LPS处理的B6小鼠相比,在妊娠第6天或第9天接受LPS处理的Jα18(-/-)小鼠的胚胎吸收率显著降低。与接受PBS处理的小鼠相比,在妊娠第6天或第9天注射LPS的B6小鼠的蜕膜iNKT细胞CD69表达以及细胞内IFN-γ和IL-17的产生显著上调。与iNKT细胞和经PBS处理的DCs共培养相比,蜕膜iNKT细胞与经LPS致敏的DCs共培养上清液中IFN-γ和IL-17的水平显著升高。与与经PBS处理的DCs共培养的iNKT细胞相比,与经LPS致敏的DCs共培养的iNKT细胞的CD69表达以及细胞内IFN-γ和IL-17的产生显著上调。

结论

我们的结果表明,iNKT细胞可能通过Th1和Th17细胞因子依赖性方式在LPS诱导的妊娠丢失中发挥作用。

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