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首页> 外文期刊>The journal of immunology >Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia
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Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia

机译：系统性增加Foxp3 +和IL-17产生的CD4 + T细胞在健康怀孕而非子痫前期的比率

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Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4+ T cells expressing Foxp3, IFN-γ, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4+CD25high, CD4+CD127lowCD25+, and CD4+Foxp3+ cells was significantly higher in normal compared with preeclamptic pregnancies. CD4+CD25high and CD4+CD127lowCD25+ populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4+Foxp3+ cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4+CD127lowCD25+ Treg cells was not significantly different between the three study groups. The percentage of CD4+IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4+IL-10- and CD4+IFN-γ-producing cells remained unchanged. Consequently, the ratio of Foxp3+ Treg to IL-17-expressing CD4+ T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3+ expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-β receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4+ T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment.
机译：子痫前症是妊娠发病率和死亡率的主要原因。尽管先兆子痫的病因尚不清楚，但据信它涉及胎儿排斥，可能是由于调节性（Treg）与效应T细胞之间的失衡。为了测试这一点，我们比较了健康和先兆子痫孕妇在妊娠晚期时表达Foxp3，IFN-γ，IL-10或IL-17的循环CD4 + T细胞的频率。与子痫前妊娠相比，正常情况下，Treg细胞区室的大小（由CD4 + CD25high，CD4 + CD127lowCD25 +和CD4 + Foxp3 +细胞的频率定义）明显更高。子痫前期的CD4 + CD25high和CD4 + CD127lowCD25 +人群与非妊娠对照组相比无显着差异，而子痫前期的CD4 + Foxp3 +细胞数量略低。在三个研究组之间，离体分选的CD4 + CD127lowCD25 + Treg细胞的抑制活性没有显着差异。与先兆子痫孕妇和未怀孕的对照组相比，健康人群中产生CD4 + IL-17的T细胞百分比显着下降，而产生CD4 + IL-10-和CD4 +IFN-γ的细胞保持不变。因此，在健康人群中，Foxp3 + Treg与表达IL-17的CD4 + T细胞的比例显着增加，但在先兆子痫妊娠中却没有。因此，先兆子痫与从IL-17产生向Foxp3 +表达的正常系统性偏斜的缺乏有关。最后，先兆子痫妇女的可溶性内皮糖蛋白水平显着升高，可溶性内皮糖蛋白是TGF-β受体信号传导的抑制剂，可能偏向IL-17的产生。这些结果表明，调节性和促炎性CD4 + T细胞之间的体内平衡可能对于在母体环境中耐受半同种异体胎儿至关重要。

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