Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (8): 24-31.doi: 10.6040/j.issn.1671-7554.0.2021.0794

Previous Articles     Next Articles

Research progress of maternal-fetal immunomodulatory mechanism

QIAO Chong, WANG Tingting   

  1. Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, Liaoning, China
  • Published:2021-09-16

RichHTML

74

PDF (PC)

886

Abstract: The maternal-fetal interface develops tolerance to the homohemiallogeneic fetus while maintaining defense against infection, which has aroused great concern in reproduction and immunology. The maternal-fetal interface is a key site for the establishment and maintenance of normal pregnancy, which is composed of trophoblast cells, decidual immune cells and decidual stromal cells. Studies on the immune mechanism of the maternal-fetal interface help to elucidate the pathogenesis of many human pregnancy complications. In this paper, the research achievements of maternal-fetal immunity in recent years are summarized, and the key cellular functions of maternal-fetal interface and the interactions between cells and cytokines are described, aiming to elaborate the mechanism of maternal-fetal immune regulation.

Key words: Maternal-fetal interface, Trophoblast cell, Decidual immune cells

CLC Number: 

  • R714.03
[1] Beaman KD, Jaiswal MK, Katara GK, et al. Pregnancy is a model for tumors, not transplantation[J]. Am J Reprod Immunol, 2016, 76(1): 3-7.
[2] Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy[J]. Nat Rev Immunol, 2017, 17(8): 469-482.
[3] Schumacher A, Sharkey DJ, Robertson SA, et al. Immune cells at the fetomaternal Interface: how the microenvironment modulates immune cells to foster fetal development[J]. J Immunol, 2018, 201(2): 325-334.
[4] Moffett A, Loke C. Immunology of placentation in eutherian mammals[J]. Nat Rev Immunol, 2006, 6(8): 584-594.
[5] Ferreira LM, Meissner TB, Mikkelsen TS, et al. A distant trophoblast-specific enhancer controls HLA-G expression at the maternal-fetal interface[J]. Proc Natl Acad Sci U S A, 2016, 113(19): 5364-5369.
[6] Gregori S, Amodio G, Quattrone F, et al. HLA-G orchestrates the early interaction of human trophoblasts with the maternal niche[J]. Front Immunol, 2015, 6: 128. doi:10.3389/fimmu.2015.00128.
[7] Ferreira LMR, Meissner TB, Tilburgs T, et al. HLA-G: at the interface of maternal-fetal tolerance[J]. Trends Immunol, 2017, 38(4): 272-286.
[8] Xu X, Zhou Y, Wei H. Roles of HLA-G in the maternal-fetal Immune microenvironment[J]. Front Immunol, 2020, 11: 592010. doi:10.3389/fimmu.2020.592010.
[9] 陈绣瑛, 黄丽丽. 人类白细胞抗原-G与母胎免疫耐受的关系[J]. 中国计划生育杂志, 2021, 29(6): 1302-1305. CHEN Xiuying, HUANG Lili. Association human leukocyte antigen-G and maternal-ketal immunotolerance[J]. Chinese Journal of Family Planning, 2021, 29(6): 1302-1305.
[10] Marcenaro E, Pesce S, Sivori S, et al. KIR2DS1-dependent acquisition of CCR7 and migratory properties by human NK cells interacting with allogeneic HLA-C2+ DCs or T-cell blasts[J]. Blood, 2013, 121(17): 3396-3401.
[11] Tilburgs T, Crespo AC, van der Zwan A, et al. Human HLA-G+ extravillous trophoblasts: immune-activating cells that interact with decidual leukocytes[J]. Proc Natl Acad Sci U S A, 2015, 112(23): 7219-7224.
[12] Papúchová H, Meissner TB, Li Q, et al. The dual role of HLA-C in tolerance and immunity at the maternal-fetal interface[J]. Front Immunol, 2019, 10: 2730. doi:10.3389/fimmu.2019.02730.
[13] Bulmer JN, Williams PJ, Lash GE. Immune cells in the placental bed[J]. Int J Dev Biol, 2010, 54(2-3): 281-294.
[14] Yang F, Zheng Q, Jin L. Dynamic function and composition changes of immune cells during normal and pathological pregnancy at the maternal-fetal interface[J]. Front Immunol, 2019, 10: 2317. doi:10.3389/fimmu.2019.02317.
[15] Le Bouteiller P, Bensussan A. Up-and-down immunity of pregnancy in humans[J]. F1000Res, 2017, 6: 1216. doi:10.12688/f1000research.11690.1.
[16] Carlino C, Stabile H, Morrone S, et al. Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy[J]. Blood, 2008, 111(6): 3108-3115.
[17] Vacca P, Vitale C, Montaldo E, et al. CD34+ hematopoietic precursors are present in human decidua and differentiate into natural killer cells upon interaction with stromal cells[J]. Proc Natl Acad Sci U S A, 2011, 108(6): 2402-2407.
[18] Manaster I, Mizrahi S, Goldman-Wohl D, et al. Endometrial NK cells are special immature cells that await pregnancy[J]. J Immunol, 2008, 181(3): 1869-1876.
[19] Ivarsson MA, Stiglund N, Marquardt N, et al. Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood[J]. Mucosal Immunol, 2017, 10(2): 322-331.
[20] Williams PJ, Searle RF, Robson SC, et al. Decidual leucocyte populations in early to late gestation normal human pregnancy[J]. J Reprod Immunol, 2009, 82(1): 24-31.
[21] 金妮, 芦洁, 王明, 等. 蜕膜自然杀伤细胞对孕早期母胎界面免疫微环境的影响[J]. 中国计划生育和妇产科, 2021, 13(7): 42-45.
[22] Gaynor LM, Colucci F. Uterine natural killer cells: functional distinctions and influence on pregnancy in humans and mice[J]. Front Immunol, 2017, 8: 467. doi:10.3389/fimmu.2017.00467.
[23] Hazan AD, Smith SD, Jones RL, et al. Vascular-leukocyte interactions: mechanisms of human decidual spiral artery remodeling in vitro[J]. Am J Pathol, 2010, 177(2): 1017-1030.
[24] Hanna J, Goldman-Wohl D, Hamani Y, et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface[J]. Nat Med, 2006, 12(9): 1065-1074.
[25] Manaster I, Mandelboim O. The unique properties of human NK cells in the uterine mucosa[J]. Placenta, 2008, 29(Suppl A): 60-66.
[26] Vento-Tormo R, Efremova M, Botting RA, et al. Single-cell reconstruction of the early maternal-fetal interface in humans[J]. Nature, 2018, 563(7731): 347-353.
[27] Fu B, Zhou Y, Ni X, et al. Natural killer cells promote fetal development through the secretion of growth-promoting factors[J]. Immunity, 2017, 47(6): 1100-1113.
[28] Tilburgs T, Evans JH, Crespo AC, et al. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface[J]. Proc Natl Acad Sci U S A, 2015, 112(43): 13312-13317.
[29] Li YH, Zhou WH, Tao Y, et al. The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy[J]. Cell Mol Immunol, 2016, 13(1): 73-81.
[30] Dempsey LA. Tim-3 promotes maternal tolerance[J]. Nat Immunol, 2017, 18(11): 1189.
[31] Liu S, Diao L, Huang C, et al. The role of decidual immune cells on human pregnancy[J]. J Reprod Immunol, 2017, 124: 44-53. doi:10.1016/j.jri.2017.10.045.
[32] Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways[J]. Cell Signal, 2014, 26(2): 192-197.
[33] Jiang X, Du MR, Li M, et al. Three macrophage subsets are identified in the uterus during early human pregnancy[J]. Cell Mol Immunol, 2018, 15(12): 1027-1037.
[34] Ning F, Liu H, Lash GE. The role of decidual macrophages during normal and pathological pregnancy[J]. Am J Reprod Immunol, 2016, 75(3): 298-309.
[35] Abrahams VM, Kim YM, Straszewski SL, et al. Macrophages and apoptotic cell clearance during pregnancy[J]. Am J Reprod Immunol, 2004, 51(4): 275-282.
[36] Grozdics E, Berta L, Bajnok A, et al. B7 costimulation and intracellular indoleamine-2,3-dioxygenase(IDO)expression in peripheral blood of healthy pregnant and non-pregnant women[J]. BMC Pregnancy Childbirth, 2014, 14: 306. doi:10.1186/1471-2393-14-306.
[37] Sayama S, Nagamatsu T, Schust DJ, et al. Human decidual macrophages suppress IFN-gamma production by T cells through costimulatory B7-H1: PD-1 signaling in early pregnancy[J]. J Reprod Immunol, 2013, 100(2): 109-117.
[38] 蒋梦琪, 王雁. 协同共刺激分子B7-H4与母胎免疫[J]. 中国生育健康杂志, 2019, 30(4): 398-400.
[39] Nancy P,Erlebacher A. T cell behavior at the maternal-fetal interface[J]. Int J Dev Biol, 2014, 58(2-4): 189-198.
[40] Tsuda S, Nakashima A, Shima T, et al. New paradigm in the role of regulatory T cells during pregnancy[J]. Front Immunol, 2019, 10: 573. doi:10.3389/fimmu.2019.00573.
[41] Wang SC, Li YH, Piao HL, et al. PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy[J]. Cell Death Dis, 2015, 6: e1738. doi:10.1038/cddis.2015.112.
[42] van Egmond A, van der Keur C, Swings GM, et al. The possible role of virus-specific CD8(+)memory T cells in decidual tissue[J]. J Reprod Immunol, 2016, 113: 1-8. doi:10.1016/j.jri.2015.09.073.
[43] Zhu JF, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations(*)[J]. Annu Rev Immunol, 2010, 28: 445-489. doi:10.1146/annurev-immunol-030409-101212.
[44] Powell RM, Lissauer D, Tamblyn J, et al. Decidual T Cells exhibit a highly differentiated phenotype and pemo- nstrate potential fetal specificity and a strong transcriptional response to IFN[J]. J Immunol, 2017, 199(10): 3406-3417.
[45] Hirahara K, Nakayama T. CD4+T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm[J]. Int Immunol, 2016, 28(4): 163-171.
[46] Wang WJ, Sung N, Gilman-Sachs A, et al. T helper(Th)cell profiles in pregnancy and recurrent pregnancy losses: Th1/Th2/Th9/Th17/Th22/Tfh cells[J]. Front Immunol, 2020, 11: 2025. doi:10.3389/fimmu.2020.02025.
[47] Taylor EB, Sasser JM. Natural killer cells and T lymphocytes in pregnancy and pre-eclampsia[J]. Clin Sci(Lond), 2017, 131(24): 2911-2917.
[48] Campbell DJ, Koch MA. Phenotypical and functional specialization of FOXP3+ regulatory T cells[J]. Nat Rev Immunol, 2011, 11(2): 119-130.
[49] Thornton AM, Korty PE, Tran DQ, et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells[J]. J Immunol, 2010, 184(7): 3433-3441.
[50] Inada K, Shima T, Ito M, et al. Helios-positive functional regulatory T cells are decreased in decidua of miscarriage cases with normal fetal chromosomal content[J]. J Reprod Immunol, 2015, 107: 10-19. doi:10.1016/j.jri.2014.09.053.
[51] Chang RQ, Li DJ, Li MQ. The role of indoleamine-2,3-dioxygenase in normal and pathological pregnancies[J]. Am J Reprod Immunol, 2018, 79(4): e12786.
[52] Miwa N, Hayakawa S, Miyazaki S, et al. IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in normal pregnancy but decrease in spontaneous abortion[J]. Mol Hum Reprod, 2005, 11(12): 865-870.
[53] Wang WJ, Liu FJ, Zhang X, et al. Periodic elevation of regulatory T cells on the day of embryo transfer is associated with better in vitro fertilization outcome[J]. J Reprod Immunol, 2017, 119: 49-53. doi:10.1016/j.jri.2017.01.002.
[54] 孙兰, 康晓敏, 武泽. CD4+T细胞在孕早期母胎界面免疫耐受中的研究进展[J]. 中国免疫学杂志, 2021, 37(6): 754-763. SUN Lan, KANG Xiaomin, WU Ze. Research progress of CD4+T cells in maternal-fetal interface immune tolerance in early pregnancy[J]. Chinese Journal of Immunology, 2021, 37(6): 754-763.
[55] 栾晓蕊, 李卫平. 滤泡性辅助T细胞亚型与原因不明复发性流产的关系研究[J]. 上海交通大学学报(医学版), 2017, 37(10): 1346-1349. LUAN Xiaorui, LI Weiping. Relationship between subtypes of T follicular helper cells and unexplained recurrent spontaneous abortion[J]. Journal of Shanghai Jiaotong University(Medical Science), 2017, 37(10): 1346-1349.
[56] Gardner L, Moffett A. Dendritic cells in the human decidua[J]. Biol Reprod, 2003, 69(4): 1438-1446.
[57] Wei R, Lai N, Zhao L, et al. Dendritic cells in pregnancy and pregnancy-associated diseases[J]. Biomed Pharmacother, 2021, 133: 110921. doi:10.1016/j.biopha.2020.110921.
[58] Tagliani E, Erlebacher A. Dendritic cell function at the maternal-fetal interface[J]. Expert Rev Clin Immunol, 2011, 7(5): 593-602. doi:10.1586/eci.11.52.
[59] Darmochwal-Kolarz DA, Kludka-Sternik M, Chmielewski T, et al. The expressions of CD200 and CD200R molecules on myeloid and lymphoid dendritic cells in pre-eclampsia and normal pregnancy[J]. Am J Reprod Immunol, 2012, 67(6): 474-481.
[60] Rieger L, Honig A, Sutterlin M, et al. Antigen-presenting cells in human endometrium during the menstrual cycle compared to early pregnancy[J]. J Soc Gynecol Investig, 2004, 11(7): 488-493.
[61] Kammerer U, Kruse A, Barrientos G, et al. Role of dendritic cells in the regulation of maternal immune responses to the fetus during mammalian gestation[J]. Immunol Invest, 2008, 37(5): 499-533.
[1] ZHONG Lili, SHENG Ying, GUO Jianghong, YANG Shuangjian, HE Yijing. LncRNA-UCA1 effects invasion and metastasis of trophoblast cells by targeting miR-182-5p [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 76-82.
[2] ZHAO Limei, YAN Lei, SHEN Xiaochang, SUN Yiqing, HE Pengjuan, ZHAO Xingbo. Effects of mifepristone and misoprostol on the expression of TRIM22 in trophoblast cells [J]. Journal of Shandong University (Health Sciences), 2019, 57(10): 86-92.
[3] JIA Xueqin1，　LIU Haiying2,　MA Yuyan2，　GAO Lingxue3, LIU Yuan2. Effects of the hepatocyte growth factor on expression of the homeobox gene HLX1 and invasion of trophoblast cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(2): 58-.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SUN Wei-peng,ZOU Wei-wei,XI Yan-wei,ZHANG Na. Oral absorption effect of liposomes with different sizes on TFu[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(6): 639 -642 .
[2] XIAO Wei-ling,LIN Ya-jie,MU Dong-zhen,SUN Ping,LIANG Shu-juan. Recombinational expression of classical pathway secreted human IL-1β in hepatoma H7402 cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(2): 119 -122 .
[3] YU Qing-mei,WU Yu-ling,SONG Hai-yan,YIN Hua-wei,ZHUANG Yuan. Expression of p38 mitogen-activated protein kinase in early embryos and the peri-implantation endometrium in mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(2): 123 -127 .
[4] ZHANG Yong,YE Jing,GUO Xin-xing,XIAO Shui-qing. Immunohistochemical expression of IL-8 in pulpal tissues on orthodontic rapid tooth movement through distraction osteogenesis of the periodontal ligament[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(4): 379 -381 .
[5] GAO Jing,CHEN Wen,ZHANG Tong-xia,WANG Xiao-hua,DAI Ting-jun,YAO Hong,ZHAO Xiu-he,CHI Zhao-fu,SHAN Pei-yan. Changes of expression of mitochondrial cytochrome oxidase subunits Ⅲ and Ⅳ in the rat hippocampus of temporal lobe epilepsy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(8): 817 -820 .
[6] . Expression and significance of stem cell marker LGR5 proteins in the  development  and progression of human colorectal carcinoma[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(8): 85 -88 .
[7] YANG Kui-zhong,SUN Xue-fei,XIANG Ji-shun,DU Qing-cong,HUANG Feng-chang. Inhibitory effect of c-FLIP-ASODN on transplantation tumor of esophagus cancer cell line EC109 in nude mice: an experimental study[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(12): 1234 -1238 .
[8] YU Xin-shuang,HAN Jun-qing,WANG Xing-wen,SHENG Wei,WANG Yu. Relationship between cytoimmunologic status and prognosis of patients with breast cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(9): 934 -937 .
[9] YU Yuan1, LI Yan1, RONG Fengnian2, LIANG Jing1, LIU Xiaolin1, WANG Fuli1. Therapy effect of auto-CIK on regulatory T cells in ovarian neoplasms patients[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(5): 101 -104 .
[10] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(7): 751 -752 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd