Placental chemokine compartmentalisation by atypical chemokine receptors.

当我们被昆虫咬伤或受伤时，我们就会在受损部位产生炎症。这涉及到白细胞的招募，白细胞可以消灭细菌，帮助伤口愈合。这些白细胞必须能够精确地找到通往受损区域的路，它们利用一种叫做趋化因子的分子来做到这一点，这种分子是在损伤或感染发生的地方产生的，它充当“灯塔”来吸引白细胞。因此，趋化因子帮助白细胞在体内找到自己的路径。趋化因子在胚胎发育中也很重要，因为白细胞和其他关键细胞必须在胚胎内移动才能正常发育。在哺乳动物中，包括人类，胚胎和母体的血液是接触的。母亲的血液中可能含有趋化因子，特别是当母亲感染或出现炎症时。因此，如果这些趋化因子能够从母体传递到胚胎，这可能会干扰它们在胚胎中的精确功能。我们一直在研究一种叫做非典型趋化因子受体的特殊分子。这些分子基本上会破坏趋化因子，它们的主要表达位点之一是胎盘中被称为滋养细胞的细胞，它位于母体和胚胎之间。基本上，这些受体破坏母体和胚胎连接处的趋化因子，确保它们不会进入胚胎循环，从而干扰发育过程中细胞运动的关键方面。我们现在想做的是用专门的老鼠模型详细研究这个过程。我们希望了解这个过程是如何运作的，以及它对胚胎存活和成人免疫和炎症功能的重要性。我们相信，这项研究的见解将对了解流产的基础以及新生儿和成人的免疫和炎症（以及潜在的神经认知）系统缺陷的各个方面非常重要。

When we are bitten by an insect, or wounded, we set up inflammation precisely at the damaged site. This involves the recruitment of cells called white blood cells to the area, which destroy bugs and help heal wounds. These white blood cells must be able to find their way precisely to the damaged area and they do this using molecules called chemokines which are made wherever damage or infection occurs and which act as a 'beacon' to attract the white blood cells. Chemokines therefore help white blood cells find their way around the body. Chemokines are also important in embryonic development as white blood cells, and other key cells, have to move within the embryo for it to develop properly. In mammals, including humans, the embryonic and maternal blood are in contact. The maternal blood can contain chemokines, especially when the mother is infected or setting up inflammation. Therefore if these chemokines were able to pass from the mother to the embryo this might interfere with their precise functions in the embryo. We have been studying specialised molecules called atypical chemokine receptors. These molecules basically destroy chemokines and one of their main sites of expression is on cells called trophoblasts in the placenta, which sit right between the mother and the embryo. Basically these receptors destroy chemokines at the junction between the mother and the embryo and ensure that they do not enter the embryonic circulation and therefore interfere with key aspects of cell movement during development. What we wish to do now is to study this process in great detail using specialised mouse models. We hope to gain an understanding of how this process functions and what its importance is for embryo survival and adult immune and inflammatory function. We believe that insights from the study will be important for understanding aspects of the basis for miscarriage and for defects in the immune and inflammatory (and potentially neuro-cognitive) systems of newborn babies and adults.