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| 1 | Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia显示文摘The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE. | Hailin Ding Yimin Dai Yi Lei Zhiyin Wang Dan Liu Ruotian Li Li Shen Ning Gu Mingming Zheng Xiangyu Zhu Guangfeng Zhao Yali Hu | 2019 | Cellular & Molecular Immunology2019，16，3： | 15 |
| 2 | Three macrophage subsets are identified in the uterus during early human pregnancy显示文摘Macrophages are crucial for a successful pregnancy, and malfunctions of decidual macrophages correlate with adverse pregnancyoutcomes, such as spontaneous abortion and preeclampsia. Previously, decidual macrophages were often thought to be a singlepopulation. In the present study, we identified three decidual macrophage subsets, CCR2−CD11cLO (CD11clow, ~80%), CCR2−CD11cHI (CD11chigh, ~5%), and CCR2+CD11cHI (CD11chigh, 10–15%), during the first trimester of human pregnancy by flowcytometry analysis. CCR2−CD11cLO macrophages are widely distributed in the decidua, while CCR2−CD11cHI and CCR2+CD11cHImacrophages are primarily detected close to extravillous trophoblast cells according to immunofluorescence staining. According toRNA sequencing bioinformatics analysis and in vitro functional studies, these three subsets of macrophages have differentphagocytic capacities. CCR2+CD11cHI macrophages have pro-inflammatory characteristics, while the CCR2−CD11cHI population issuggested to be anti-oxidative and anti-inflammatory due to its high expression of critical heme metabolism-related genes,suggesting that these two subsets of macrophages maintain an inflammatory balance at the leading edge of trophoblast invasionto facilitate the clearance of pathogen infection as well as maintain the homeostasis of the maternal-fetal interface. The presentstudy physiologically identifies three decidual macrophage subsets. Further clarification of the functions of these subsets willimprove our understanding of maternal-fetal crosstalk in the maintenance of a healthy pregnancy. | Xiangxiang Jiang Mei-Rong Du Min Li Hongmei Wang | 2018 | Cellular & Molecular Immunology2018，15，12： | 15 |
| 3 | 复发性流产相关基因的生物信息学分析显示文摘目的归纳复发性流产相关基因的文献,并进行生物信息学分析,为进一步的研究和临床治疗提供参考依据。方法检索CNKI、万方、Pubmed数据库从2005年1月1日—2018年5月30日发表的文献,统计出复发性流产的相关基因,并用DAVID在线数据库对基因进行基因本体论(GO)富集分析、京都基因与基因组百科(KEGG)通路分析,STRING在线数据库构建蛋白-蛋白互作网络图(PPI),Cytoscape 3.7.0软件进行可视化分析。结果筛选出674篇文献,摘录复发性流产相关基因170个,DAVID不同分类149种,KEGG通路60种,这些基因主要参与炎症反应、免疫应答、RNA聚合酶II启动子转录的正调控/负调控、血管生成、T细胞增殖等有关。KEGG通路主要是参与癌症中的蛋白聚糖、细胞因子-细胞因子受体相互作用、Jak-STAT信号通路、HIF-1信号通路、炎症性肠病、内风湿关节炎等。其中129个参与构建PPI,进一步可视化分析筛选出节点度数排前10的基因:IL6、IL10、VEGFA、TGFβ1、IFNG、TP53、IL1β、STAT3、CCL2、TLR4。结论所筛选复发性流产的关键基因有助于进一步研究该病的发病机制,同时为药物防治该病提供新的靶点。 | 奚婷 包晓霞 许梦白 刘柳青 刘雁峰 | 2020 | 中华中医药学刊2020，38，5： | 4 |
| 4 | CD14+HLA-DRLow/-髓源抑制性细胞样细胞与白细胞介素1β在卵巢癌中的表达及相关性显示文摘目的 分析卵巢癌患者外周血及腹水CD14+ HLA-DRLow/-髓源抑制性细胞(MDSCs)样细胞与白细胞介素1β(IL-1β)的表达水平,探讨与卵巢癌临床病理特征的相关性.方法 收集2016年1至12月山东大学齐鲁医院31例卵巢癌患者外周血,从中选取5例中晚期患者留取腹腔积液.收集同一时期年龄构成相匹配的20名健康志愿者外周血作为对照.流式细胞术分析卵巢癌患者外周血、腹腔积液以及健康对照者外周血中CD14+ HLA-DRLow/-细胞亚群在CD14+单核细胞中所占比例并分离获取该群细胞.流式细胞术分析CD14+ HLA-DRLow/-细胞亚群表型,实时定量PCR检测该群细胞免疫抑制因子表达情况.酶联免疫吸附法检测卵巢癌患者外周血、腹腔积液以及健康对照者外周血中IL-1 β表达水平,并与CD14+ HLA-DRLow/-细胞所占比例进行相关性分析.统计卵巢癌患者临床资料,分析CD14+ HLA-DRLow/-细胞及IL-1β水平与临床病理特征的相关性.结果 健康对照组及卵巢癌患者外周血CD14+ HLA-DRLow/-细胞在CD14+单核细胞中所占比例分别为(2.30±0.49)%和(3.74±0.95)%,差异有统计学意义(t =6.96,P<0.01),该群细胞表型与因子表达与单核样MDSCs相似.卵巢癌患者腹腔积液中CD14+ HLA-DRLow/-细胞百分比为(16.60±7.35)%,显著高于外周血的(4.03±0.94)%,差异有统计学意义(t =3.87,P<0.05).健康对照组及卵巢癌患者外周血IL-1β水平分别为3.88(0.41,7.07) ng/L及(12.77±3.52) ng/L,差异有统计学意义(Z=-4.93,P<0.01).5例卵巢癌患者腹腔积液IL-1β水平为(62.17 ±23.05) ng/L,显著高于外周血的(12.65 ±3.93) ng/L,差异有统计学意义(=5.20,P<0.01).卵巢癌患者外周血及腹腔积液IL-1β表达水平与CD14+ HLA-DRLow/-细胞比例存在相关性(外周血R2 =0.36,P<0.01;腹腔积液R2=0.68,P<0.05),健康对照组外周血IL-1β表达水平与CD14+ HLA-DRLow/-细胞比例无相关性(R2=0.02,P>0.05).CD14+ HLA-DRLow/-细胞及IL-1β水平与卵巢癌浸润转移及FIGO分期有关.结论 卵巢癌患者CD14+ HLA-DRLow/-细胞及IL-1β存在异常表达,可能与卵巢癌的发展有关. | 王华阳 赵睿 任浩 邹明瑾 张建 张义 | 2017 | 中华医学杂志2017，97，34： | 4 |
| 5 | 髓源性抑制细胞在母胎界面的免疫调节作用显示文摘髓源性抑制细胞(myeloid derived suppressor cell, MDSC)指一群髓系来源的未成熟异质性免疫抑制细胞,其研究多集中于肿瘤、感染和自身免疫性疾病。近年来研究发现,MDSC也参与母胎免疫,尤其是粒细胞样髓源性抑制细胞(granulocyte like myeloid derived suppressor cell, G-MDSC)的数量增加在母胎免疫动态平衡和生理环境(如正常妊娠)中表现出有益作用,在胎盘形成、胎儿生长和发育中起着关键作用。妊娠期间MDSC的缺失或调节失衡与妊娠相关并发症密切相关。脐带血和新生儿体内亦有大量MDSC,它们可平衡免疫反应并防止新生儿的侵袭性炎症反应。因此,该综述旨在阐明有关MDSC的基本特征,并讨论它们在母胎界面和妊娠相关并发症中的可能作用。 | 黄丹 崔树娜 | 2021 | 现代免疫学2021，41，6： | 3 |
| 6 | Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development显示文摘The maternal immune system is vital in maintaining immunotolerance to the semiallogeneic fetus for a successful pregnancy.Although studies have shown that myeloid-derived suppressor cells(MDSCs)play an important role in maintaining feto-maternal tolerance,little is known about the role of MDSCs in pregnancies with intrauterine growth retardation(IUGR).Here,we reported that the activation of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)during pregnancy was closely associated with fetal growth.In humans,class E scavenger receptor 1(SR-E1),a distinct marker for human PMN-MDSCs,was used to investigate PMN-MDSC function during pregnancy.Continuous activation of SR-E1+PMN-MDSCs was observed in all stages of pregnancy,accompanied by high cellular levels of ROS and arginase-1 activity,mediated through STAT6 signaling.However,SR-E1+PMN-MDSCs in pregnancies with IUGR showed significantly lower suppressive activity,lower arginase-1 activity and ROS levels,and decreased STAT6 phosphorylation level,which were accompanied by an increase in inflammatory factors,compared with those in normal pregnancies.Moreover,the population of SR-E1+PMN-MDSCs was negatively correlated with the adverse outcomes of newborns from pregnancies with IUGR.In mice,decreases in cell population,suppressive activity,target expression levels,and STAT6 phosphorylation levels were also observed in the pregnancies with IUGR compared with the normal pregnancies,which were rescued by the adoptive transfer of PMN-MDSCs from pregnant mice.Interestingly,the growth-promoting factors(GPFs)secreted by placental PMN-MDSCs in both humans and mice play a vital role in fetal development.These findings collectively support that PMN-MDSCs have another new role in pregnancy,which can improve adverse neonatal outcomes. | Mengyu Shi Ziyang Chen Meiqi Chen Jingping Liu Jing Li Zhe Xing Xiaogang Zhang Shuaijun Lv Xinyao Li Shaowen Zuo Shi Feng Ying Lin Gang Xiao Liping Wang Yumei He | 2021 | Cellular & Molecular Immunology2021，18，7： | 1 |
| 7 | 髓系来源的抑制性细胞在母-胎界面的研究进展显示文摘髓系来源的抑制性细胞(myeloid derived suppressor cells,MDSCs)是一类具有显著抑制T细胞功能的异质性细胞群体,能够促进机体免疫耐受形成。在妊娠建立过程中,母体免疫系统要对含有父系抗原的胎儿具有足够的免疫耐受,具有免疫抑制特性的细胞以及细胞因子在母-胎界面聚集是母-胎免疫耐受形成的机制之一。近年来,有研究表明MDSCs在母-胎界面聚集,促进母-胎免疫耐受的形成。本文就MDSCs的免疫抑制特性及其在妊娠中的研究进展作一综述。 | 胡晓惠 廖爱华 | 2018 | 中华生殖与避孕杂志2018，38，1： | 0 |
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