Effects of HLA-G on accumulation of myeloid-derived suppressor cells (MDSC) and successful pregnancy

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Miscarriage is the most important pregnancy complication, affecting up to 50% of women. Maternal immune system plays an important role in pathogenesis of miscarriage. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells and are known to accumulate during pregnancy. It was hypothesized that MDSC are important for maintenance of maternal-fetal tolerance and successful pregnancy. Until now, only little is known about factors regulating MDSC accumulation and function during pregnancy. Human leucocyte antigen (HLA) G is expressed during pregnancy by cells of the fetal placenta. It regulates various immune functions in order to avoid rejection of the fetus by maternal immune cells. In this project, we aim to prove the hypothesis that HLA-G induces MDSC during pregnancy thereby preventing miscarriage. In a clinical study we aim to analyze correlation between levels of soluble HLA-G (sHLA-G) and MDSC numbers. In in vitro experiments with murine cells the effect of sHLA-G on MDSC-function will be investigated. Last, it will be examined how lack of HLA-G, respectively its murine correlate Qa2, affects murine pregnancy and if application of HLA-G can reduce incidence of abortions in two in vivo mouse models. The results of the study can help to a better understanding of immunological processes leading to pregnancy failure and to develop therapeutic strategies for prevention of miscarriage.