Tuebingen University Children's Hospital, Department of Neonatology, Tuebingen, Germany.
Department of Dermatology, University of Tuebingen, Tuebingen, Germany.
Cell Immunol. 2021 Mar;361:104276. doi: 10.1016/j.cellimm.2020.104276. Epub 2020 Dec 24.
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不完全清楚，治疗选择有限。髓源性抑制细胞（MDSC）是在健康妊娠期间扩增的免疫调节细胞，似乎对母胎耐受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的病理条件下具有与其亲本细胞相应的免疫调节作用。在这里，我们研究了妊娠期间 GR-MDSC 外泌体的免疫学效应。从孕妇外周血中分离出的 GR-MDSC 外泌体在不同的体外实验中进行了功能测试。我们表明，GR-MDSC 外泌体表现出深刻的免疫调节作用，如抑制 T 细胞增殖、辅助性 T 细胞 2（Th2）极化、诱导调节性 T 细胞和抑制淋巴细胞细胞毒性。我们的结果证实，MDSC 衍生的外泌体在功能上与其亲本细胞相对应，并将其鉴定为免疫性妊娠并发症的一个有趣的治疗靶点。
