Immunological pregnancy complications are a main challenge in reproductive medicine. Mechanisms regulating the adaptation of the maternal immune system to pregnancy are incompletely understood and therapeutic options limited. Myeloid derived suppressor cells (MDSC) are immune-modulatory cells expanding during healthy pregnancy and seem to play a crucial role for maternal-fetal tolerance. Recent studies showed that exosomes produced by MDSC have immune-modulatory effects corresponding to their parental cells under different pathological conditions. Here, we investigated immunological effects of exosomes of GR-MDSC during pregnancy. Isolated GR-MDSC exosomes from peripheral blood of pregnant women were tested for functionality in different in vitro assays. We show that GR-MDSC exosomes exhibited profound immune-modulatory effects such as suppression of T-cell proliferation, T helper 2 (Th2)-cell polarization, induction of regulatory T-cells and inhibition of lymphocyte cytotoxicity. Our results confirm that MDSC-derived exosomes functionally correspond to their parental cells and identify them as an interesting therapeutic target for immunological pregnancy complications.

免疫性妊娠并发症是生殖医学的主要挑战。调节母体免疫系统适应妊娠的机制尚未完全了解，治疗选择受到限制。髓样来源的抑制细胞（MDSC）是在健康怀孕期间扩增的免疫调节细胞，似乎对母胎耐受性起着至关重要的作用。最近的研究表明，MDSC产生的外泌体在不同病理条件下具有与其亲代细胞相对应的免疫调节作用。在这里，我们调查了怀孕期间GR-MDSC外泌体的免疫学作用。从孕妇外周血中分离出的GR-MDSC外泌体在不同体外测试了功能分析。我们表明，GR-MDSC外泌体表现出深刻的免疫调节作用，例如抑制T细胞增殖，T辅助2（Th2）细胞极化，诱导调节性T细胞和抑制淋巴细胞的细胞毒性。我们的研究结果证实，MDSC衍生的外泌体在功能上对应于其亲代细胞，并将其鉴定为免疫性妊娠并发症的有趣治疗靶标。