Placental chemokine compartmentalisation by atypical chemokine receptors.

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.