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

流产是最重要的妊娠并发症，影响高达50%的妇女。母体免疫系统在流产发病机制中起重要作用。髓系抑制细胞(MDSC)是一种髓系细胞，对其他免疫细胞具有抑制活性，已知在怀孕期间积聚。推测MDSC对于维持母胎耐受性和成功妊娠具有重要意义。到目前为止，对妊娠期间调节MDSC积累和功能的因素知之甚少。人类白细胞抗原(HLAG)在妊娠期间由胎儿胎盘细胞表达。它调节各种免疫功能，以避免母体免疫细胞对胎儿的排斥。在这个项目中，我们的目标是证明这一假设，即人类白细胞抗原-G在怀孕期间诱导MDSC，从而防止流产。在一项临床研究中，我们旨在分析可溶性人类白细胞抗原-G(sHLA-G)水平与骨髓间充质干细胞数量的相关性。在小鼠细胞的体外实验中，将研究sHL A-G对MDSC功能的影响。最后，将在两个活体小鼠模型中检验缺乏与其小鼠QA2相关的人类白细胞抗原-G是如何影响小鼠怀孕的，以及应用人类白细胞抗原-G是否可以减少流产的发生率。研究结果有助于更好地了解导致妊娠失败的免疫学过程，并制定预防流产的治疗策略。

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.