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早产儿出生后炎症性和调节性脐血细胞之间的失衡。

Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth.

机构信息

Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.

University Hospital for Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.

出版信息

J Reprod Immunol. 2021 Jun;145:103319. doi: 10.1016/j.jri.2021.103319. Epub 2021 Apr 8.

DOI:10.1016/j.jri.2021.103319
PMID:33848896
Abstract

Preterm birth (PTB) is one of the most frequent pregnancy complications. It affects millions of babies each year worldwide and is associated with increased morbidity and mortality. PTB-associated alterations in the maternal immune response may have a direct effect on the developing fetal immune system. Having recently shown that B regulatory (Breg) cells are decreased in number and functionally impaired in maternal blood from women delivering preterm, we now addressed the question whether the adaptive immune system is also altered in cord blood (CB) after the onset of PTB. PTB was associated with increased concentrations of IL-6, TNF-α and IL-21 in CB and enhanced IL-6, but decreased IFN-γ and IL-4 in amniotic fluid (AF) samples compared to term delivery (TD). We found no differences in the frequency of CD19 + B cells, CD4 + T cells or CD4+Foxp3+CD25+ T regulatory (Treg) cells in CB cells in PTB vs TD. The frequency of CD86 + B cells was increased, while the percentage of CD24CD38CD19 + Breg and CD1dCD5+ Breg cells and the ability of B cells to convert into Breg cells was diminished in PTB compared to TD. CB B cells from PTB secreted more IL-6, TNF-α, IL-9 and IL-2 compared to B cells obtained from term samples. We conclude that, after PTB onset, a shift from immunoregulation towards inflammation takes place in CB cells that are reportedly representative of the fetal compartment. B cells have a substantial contribution herein. This phenomenon might account for the observed enhanced mortality and morbidity in prematurely born infants. Further studies will clarify how to employ this easy-to-obtain information for closely monitoring newborns at risk.

摘要

早产(PTB)是最常见的妊娠并发症之一。它每年在全球影响数百万婴儿,并与发病率和死亡率增加有关。与 PTB 相关的母体免疫反应改变可能对正在发育的胎儿免疫系统产生直接影响。我们最近表明,早产妇女的母血中 B 调节(Breg)细胞数量减少且功能受损,现在我们研究了 PTB 后脐带血(CB)中的适应性免疫系统是否也发生改变。与足月分娩(TD)相比,PTB 与 CB 中 IL-6、TNF-α 和 IL-21 浓度增加以及羊水中 IL-6 增强而 IFN-γ 和 IL-4 减少有关。与 TD 相比,我们在 PTB 中 CB 细胞中未发现 CD19+B 细胞、CD4+T 细胞或 CD4+Foxp3+CD25+T 调节(Treg)细胞的频率存在差异。CD86+B 细胞的频率增加,而 CD24CD38CD19+Breg 和 CD1dCD5+Breg 细胞的百分比以及 B 细胞转化为 Breg 细胞的能力在 PTB 中低于 TD。与从足月样本获得的 B 细胞相比,PTB 的 CB B 细胞分泌更多的 IL-6、TNF-α、IL-9 和 IL-2。我们得出结论,PTB 发作后,CB 细胞中从免疫调节向炎症的转变发生,据报道 CB 细胞代表胎儿隔室。B 细胞在此中有很大的贡献。这种现象可能解释了早产儿观察到的死亡率和发病率增加。进一步的研究将阐明如何利用这种易于获得的信息来密切监测有风险的新生儿。

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