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Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth
Journal of Reproductive Immunology ( IF 2.9 ) Pub Date : 2021-04-08 , DOI: 10.1016/j.jri.2021.103319
Mandy Busse 1 , Anke Redlich 2 , Roland Hartig 3 , Serban-Dan Costa 2 , Henning Rathert 4 , Stefan Fest 5 , Ana Claudia Zenclussen 6
Affiliation  

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 CD24hiCD38hiCD19 + Breg and CD1dhiCD5+ 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.



中文翻译:

早产后炎症性和调节性脐带血 B 细胞之间的失衡

早产 (PTB) 是最常见的妊娠并发症之一。它每年影响全球数百万婴儿,并与发病率和死亡率增加有关。

母体免疫反应中 PTB 相关的改变可能对发育中的胎儿免疫系统有直接影响。最近表明,早产妇女的母体血液中 B 调节 (Breg) 细胞数量减少且功能受损,我们现在解决了 PTB 发病后脐带血 (CB) 中适应性免疫系统是否也发生改变的问题。

与足月分娩 (TD) 相比,PTB 与 CB 中 IL-6、TNF-α 和 IL-21 的浓度增加和 IL-6 增加有关,但羊水 (AF) 样品中的 IFN-γ 和 IL-4 减少。我们发现 PTB 与 TD 中 CB 细胞中 CD19 + B 细胞、CD4 + T 细胞或 CD4 + Foxp3 + CD25 + T 调节 (Treg) 细胞的频率没有差异。与 TD 相比,PTB中 CD86 + B 细胞的频率增加,而 CD24 hi CD38 hi CD19 + Breg 和 CD1d hi CD5+ Breg 细胞的百分比以及 B 细胞转化为 Breg 细胞的能力降低。与从足月样本获得的 B 细胞相比,来自 PTB 的 CB B 细胞分泌更多的 IL-6、TNF-α、IL-9 和 IL-2。

我们得出的结论是,在 PTB 发病后,CB 细胞发生了从免疫调节到炎症的转变,据报道,这些细胞代表了胎儿区室。B细胞在此具有重要贡献。这种现象可能是观察到的早产婴儿死亡率和发病率增加的原因。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处于危险中的新生儿。

更新日期:2021-04-11
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