Habbeddine Mohamed, Verbeke Philippe, Karaz Sonia, Bobé Pierre, Kanellopoulos-Langevin Colette
Laboratory of Inflammation, Gestation and Autoimmunity, Jacques Monod Institute, CNRS and University Paris-Diderot, Paris, France.
Genetics and development of the cerebral cortex, Jacques Monod Institute, CNRS and University Paris-Diderot, Paris, France.
PLoS One. 2014 Sep 26;9(9):e107267. doi: 10.1371/journal.pone.0107267. eCollection 2014.
Despite much interest in the mechanisms regulating fetal-maternal interactions, information on leukocyte populations and major cytokines present in uterus and placenta remains fragmentary. This report presents a detailed and quantitative study of leukocyte populations at the mouse fetal-maternal interface, including a comparison between pregnancies from syngeneic and allogeneic crosses. Our results provide evidence for drastic differences not only in the composition of leukocyte populations in the uterus during pregnancy, but also between uterine and placental tissues. Interestingly, we have observed a significant decrease in the number of myeloid Gr1+ cells including monocytes, and myeloid CD11c+ cells including DCs in placenta from an allogeneic pregnancy. In addition, we have compared the expression levels of a panel of cytokines in non-pregnant (NP) or pregnant mouse uterus, in placenta, or in their isolated resident leukocytes. Qualitative and quantitative differences have emerged between NP, pregnant uterus and placenta. Unexpectedly, IL-9 was the major cytokine in NP uterus, and was maintained at high levels during pregnancy both in uterus and placenta. Moreover, we have found that pregnancy is associated with an increase in uterine IL-1a and a significant decrease in uterine G-CSF and GM-CSF. Comparing allogeneic versus syngeneic pregnancy, less allogeneic placental pro-inflammatory cytokines CCL2 (MCP-1), CXCL10 (IP-10) and more IL1-α in whole uterus was reproducibly observed. To our knowledge, this is the first report showing a detailed overview of the leukocyte and cytokine repertoire in the uterus of virgin females and at the fetal-maternal interface, including a comparison between syngeneic and allogeneic pregnancy. This is also the first evidence for the presence of IL-9 in NP uterus and at the maternal-fetal interface, suggesting a major role in the regulation of local inflammatory or immune responses potentially detrimental to the conceptus.
尽管人们对调节胎儿与母体相互作用的机制非常感兴趣，但关于子宫和胎盘中白细胞群体及主要细胞因子的信息仍然支离破碎。本报告对小鼠胎儿与母体界面处的白细胞群体进行了详细的定量研究，包括对同基因和异基因杂交妊娠的比较。我们的结果不仅证明了孕期子宫中白细胞群体组成存在显著差异，还表明子宫组织和胎盘组织之间也存在差异。有趣的是，我们观察到异基因妊娠胎盘内包括单核细胞的髓样Gr1+细胞以及包括树突状细胞的髓样CD11c+细胞数量显著减少。此外，我们比较了非妊娠（NP）或妊娠小鼠子宫、胎盘及其分离的驻留白细胞中一组细胞因子的表达水平。NP、妊娠子宫和胎盘之间出现了定性和定量差异。出乎意料的是，IL-9是NP子宫中的主要细胞因子，在孕期子宫和胎盘中均维持在高水平。此外，我们发现妊娠与子宫IL-1α增加以及子宫G-CSF和GM-CSF显著减少有关。比较异基因妊娠与同基因妊娠，可重复性地观察到异基因胎盘促炎细胞因子CCL2（MCP-1）、CXCL10（IP-10）减少，而全子宫中IL1-α增多。据我们所知，这是第一份详细概述未孕雌性小鼠子宫和胎儿与母体界面处白细胞和细胞因子库的报告，包括同基因和异基因妊娠的比较。这也是首次证明NP子宫和母胎界面存在IL-9，提示其在调节可能对胚胎有害的局部炎症或免疫反应中起主要作用。
