Immune tolerance in human pregnancy; how it materialises and its clinical exploitation

Tolerance of the human fetus in the womb, and specifically the placenta, remains an undefined paradox of human pregnancy. Although genetic differences should render it susceptible to maternal immune attack; not only is the placenta actively tolerated, the resultant immunological changes instigate improvements in graft and transplant acceptance and laudable reductions in inflammatory conditions, such as rheumatoid arthritis (1). Thus, better knowledge may hold advances over current immunosuppressive therapies, as well as ways of preventing fetal rejection, through stillbirth or miscarriage.

To date, all investigations of maternal immune interactions with the human placenta have focused on distant events, in time and location, from the point where tolerance is instigated, i.e. first contact between embryo and uterus. Using new organoid culture techniques, and other physiological models of embryo-uterine interactions, we are now in a position to study the early stages of human pregnancy and implantation with regard to maternal immune cell recognition and involvement.

In these studies, dendritic cells of the uterus will be prioritised, through their capacity to direct maternal T cells and influence immune privilege. Alongside mechanistic studies, in vivo models of induced-arthritis will be used to define the immunosuppressive potential of placental-derived factors at the whole body level, bridging the gap between local tolerogenic reprogramming and clinical graft acceptance and inflammatory amelioration.

Success will not only help address the century’s-old paradox of human pregnancy, but also define causes of unexplained fetal loss and novel avenues for inflammation and immune-suppression.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a topic related to biological and medical sciences. Candidates with experience in cell biology, development or immunology or with an interest in reproductive medicine are encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Medicine

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international-phd/