Prevention of CpG-induced pregnancy disruption by adoptive transfer of in vitro-induced regulatory T cells.
Prevention of CpG-induced pregnancy disruption by adoptive transfer of in vitro-induced regulatory T cells.
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通过体外诱导的调节性 T 细胞过继转移来预防 CpG 诱导的妊娠中断
DOI：
10.1371/journal.pone.0094702
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sun Y
中科院分区：
文献类型：
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作者：
Lin Y;Liu X;Shan B;Wu J;Sharma S;Sun Y
为阐明致病性CpG基序加剧胚胎吸收和早产的机制，并制定实现正常妊娠结局的应对策略。
这是一项基于动物模型的研究。在怀孕的非肥胖糖尿病（NOD）小鼠以及具有相同品系背景的野生型（WT）小鼠中，通过注射CpG1826激活Toll样受体9（TLR9）来模拟感染。体内使白细胞介素 - 10（IL - 10）失活以加剧妊娠丢失。将体外由FTY720从脾脏CD4 + CD25 - Foxp3 - 细胞诱导产生的调节性T细胞（iTreg细胞）进行过继转移，以改善NOD小鼠的妊娠结局。
在NOD小鼠中，CpG1826很容易诱导胚胎吸收和早产，但在WT小鼠中则不会。然而，通过注射中和抗体使IL - 10失活，会加剧暴露于CpG的WT小鼠的妊娠丢失，而iTreg细胞的过继转移增加了蜕膜中Foxp3 +调节性T细胞和IL - 10 +细胞的数量，并挽救了妊娠。
NOD小鼠易发生流产和早产。这可归因于调节性T细胞缺乏和IL - 10表达不足。iTreg细胞的过继转移可以挽救由CpG介导的妊娠失败。
Objective To elucidate the mechanism by which embryo-resorption and preterm birth were enhanced by pathogenic CpG motif and to develop a counter strategy for normal pregnancy outcome. Methods This is an animal model-based study. In pregnant nonobese diabetic (NOD) mice and wild-type (WT) mice in the same strain background, an infection was mimicked by toll-like receptor 9 (TLR9) activation through CpG1826-injection. In vivo inactivation of IL-10 was performed to enhance pregnancy loss. Regulatory T cells induced by FTY720 in vitro from splenic CD4+CD25−Foxp3− cells (iTreg cells) were transferred to improve pregnancy outcomes in NOD mice. Results Embryo-resorption and preterm birth were readily induced by CpG1826 in NOD mice, but not in WT mice. However, inactivation of IL-10 using neutralizing antibody injections enhanced pregnancy loss in WT mice exposed to CpG, while adoptive transfer of iTreg cells increased decidual Foxp3+ Treg cells and IL-10+ cell number and rescued pregnancy. Conclusions NOD mice are prone to abortion and preterm birth. This can be attributed to lacking Treg cells and insufficient IL-10 expression. Adoptive transfer of iTreg cells can rescue CpG-mediated pregnancy failure.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
9.8
作者：
Murphy, Shaun P.;Hanna, Nazeeh N.;Fast, Loren D.;Shaw, Sunil K.;Berg, Goeran;Padbury, James F.;Romero, Roberto;Sharma, Surendra
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影响因子：
3.4
作者：
Lin, Yi;Ren, Lingling;Saito, Shigeru
通讯作者：
Saito, Shigeru
影响因子：
64.5
作者：
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