Sydney Medical School Nepean, University of Sydney, Kingswood 2751, New South Wales, Australia.
J Immunol. 2013 Jul 1;191(1):145-53. doi: 10.4049/jimmunol.1203165. Epub 2013 Jun 3.
Transplacental immune regulation refers to the concept that during pregnancy, significant cross-talk occurs between the maternal and fetal immune system with potential long-term effects for both the mother and child. In this study, we made the surprising observation that there is a strong correlation of peripheral blood regulatory T (Treg) cells between the mother and the fetus. In contrast, there is no significant Treg cell correlation between paternal fetal dyads (pairs), suggesting that the specific context of pregnancy, rather than the genetic parental similarity to the fetus, is responsible for this correlation. Gene microarray analysis of Treg cells identified a typical IL-10-dependent signature in maternal and fetal Treg cells. In addition, a direct correlation of serum IL-10 protein levels between maternal fetal dyads was observed. Furthermore, we show that maternal serum IL-10 levels correlate with serum estradiol and estriol, implicating hormonal involvement in this alignment. Interestingly, we show that Treg cells possess higher expression of IL-10 receptor α and that Treg cell IL-10 receptor α expression directly correlates with their Bcl-2 expression. Indeed, in vitro data in both humans and mice demonstrate that IL-10 upregulates Bcl-2 specifically in Treg cells but not non-Treg cells. Our results provide evidence for transplacental regulation of cellular immunity and suggest that IL-10 may influence Treg cell homeostasis through its effect on Treg cell Bcl-2 expression. These novel findings have important implications on immune tolerance in pregnancy and beyond in areas of autoimmunity, allergy, and transplantation.
胎盘免疫调节是指在妊娠期间，母体和胎儿免疫系统之间发生显著的串扰，对母婴双方都可能产生长期影响。在这项研究中，我们惊奇地发现，母亲和胎儿外周血调节性 T（Treg）细胞之间存在强烈的相关性。相比之下，父胎二联体（对子）之间的 Treg 细胞没有显著的相关性，这表明这种相关性与妊娠的特定环境有关，而与胎儿的遗传父母相似性无关。对 Treg 细胞的基因微阵列分析鉴定出母体和胎儿 Treg 细胞中存在典型的 IL-10 依赖性特征。此外，还观察到母胎对子之间血清 IL-10 蛋白水平存在直接相关性。此外，我们还表明，母体血清 IL-10 水平与血清雌二醇和雌三醇相关，提示激素参与了这种一致性。有趣的是，我们发现 Treg 细胞具有更高的 IL-10 受体α表达，并且 Treg 细胞的 IL-10 受体α表达与其 Bcl-2 表达直接相关。实际上，在人类和小鼠的体外数据表明，IL-10 特异性地上调 Treg 细胞而不是非 Treg 细胞中的 Bcl-2。我们的研究结果为细胞免疫的胎盘调节提供了证据，并表明 IL-10 可能通过其对 Treg 细胞 Bcl-2 表达的影响来影响 Treg 细胞的稳态。这些新发现对妊娠期间及自身免疫、过敏和移植等领域的免疫耐受具有重要意义。
