母胎免疫中巨噬细胞作用机制的研究进展
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摘要
胚泡植入是妊娠过程中的关键步骤,包括胚泡在子宫内膜的定位、黏附和侵入。对于母体子宫来说,胚泡是一种半同种异型移植物,植入成功与否依赖于母体子宫免疫细胞对胚泡的识别,以及随后对其建立和维持的免疫耐受。巨噬细胞是母胎交流中的第二大类免疫细胞,在母胎界面免疫耐受的建立、维持,组织重建以及螺旋动脉重塑过程中发挥关键作用。近年来,许多研究发现巨噬细胞分化和功能异常与病理性妊娠有关,而研究蜕膜巨噬细胞的种类和功能对妊娠异常性疾病的诊断与治疗均有重要的意义。综述母胎界面中巨噬细胞的来源、分类及其在胚泡植入和病理性妊娠过程中作用。
Blastocyst implantation is a critical stage in the pregnancy process, including apposition, adhesion and invasion of blastocysts in the endometrium. The blastocyst is a semi-allogeneic transplant for the uterus. The successful implantation dependents on the immune tolerance established and maintained by maternal immune cells located in the uterus.As the second largest immune cell group at the maternal-fetal interface, macrophages play a critical role in establishing and maintaining maternal-fetal immune tolerance and remodeling tissue and spiral arteries. Recent studies have found that abnormal differentiation or dysfunction of macrophages is significantly correlated with pathological pregnancy. Thus, studies on the types and functions of decidual macrophages will help us to improve the diagnosis and treatment of pathologic pregnancy. This review is mainly focused on research progresses in the derivation and classification of macrophages at the maternal-fetal interface as well as the roles of the macrophages in blastocyst implantation and pathological pregnancy.
Blastocyst implantation is a critical stage in the pregnancy process, including apposition, adhesion and invasion of blastocysts in the endometrium. The blastocyst is a semi-allogeneic transplant for the uterus. The successful implantation dependents on the immune tolerance established and maintained by maternal immune cells located in the uterus.As the second largest immune cell group at the maternal-fetal interface, macrophages play a critical role in establishing and maintaining maternal-fetal immune tolerance and remodeling tissue and spiral arteries. Recent studies have found that abnormal differentiation or dysfunction of macrophages is significantly correlated with pathological pregnancy. Thus, studies on the types and functions of decidual macrophages will help us to improve the diagnosis and treatment of pathologic pregnancy. This review is mainly focused on research progresses in the derivation and classification of macrophages at the maternal-fetal interface as well as the roles of the macrophages in blastocyst implantation and pathological pregnancy.
引文
[1]中国卫计委.中国年均完成辅助生殖技术治疗70万例[EB/OL].2016-03-03.http://www.chinanews.com/jk/2016/03-08/7789190.shtml.
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[3]Care AS,Diener KR,Jasper MJ,et al.Macrophages regulate corpus luteum development during embryo implantation in mice[J].J Clin Invest,2013,123(8):3472-3487.
[4]Mor G,Cardenas I,Abrahams V,et al.Inflammation and pregnancy:the role of the immune system at the implantation site[J].Ann NYAcad Sci,2011,1221:80-87.
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[9]Mantovani A,Sica A,Sozzani S,et al.The chemokine system in diverse forms of macrophage activation and polarization[J].Trends Immunol,2004,25(12):677-686.
[10]Martinez FO,Gordon S,Locati M,et al.Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization:new molecules and patterns of gene expression[J].J Immunol,2006,177(10):7303-7311.
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[12]Italiani P,Boraschi D.From Monocytes to M1/M2 Macrophages:Phenotypical vs.Functional Differentiation[J].Front Immunol,2014,5:514.
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[14]Vomhof-DeKrey E,Darland D,Ghribi O,et al.Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFαexpression in Sprague-Dawley rats[J].JReprod Immunol,2016,118:9-17.
[15]Lash GE,Pitman H,Morgan HL,et al.Decidual macrophages:key regulators of vascular remodeling in human pregnancy[J].J Leukoc Biol,2016,100(2):315-325.
[16]Fu B,Wei H.Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface[J].Sci China Life Sci,2016,59(12):1224-1231.
[17]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.
[18]Krausgruber T,Blazek K,Smallie T,et al.IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses[J].Nat Immunol,2011,12(3):231-238.
[19]Svensson J,Jenmalm MC,Matussek A,et al.Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10[J].J Immunol,2011,187(7):3671-3682.
[20]Svensson-Arvelund J,Mehta RB,Lindau R,et al.The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages[J].JImmunol,2015,194(4):1534-1544.
[21]Smith SD,Dunk CE,Aplin JD,et al.Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy[J].Am J Pathol,2009,174(5):1959-1971.
[22]高瑞花,陈雷宁,谭雯雅,等.围着床期小鼠子宫中巨噬细胞的变化及作用[J].南方医科大学学报,2015,35(3):365-369.
[23]Toda N,Toda H,Okamura T.Regulation of myometrial circulation and uterine vascular tone by constitutive nitric oxide[J].Eur JPharmacol,2013,714(1/2/3):414-423.
[24]Buckley RJ,Whitley GS,Dumitriu IE,et al.Macrophage polarisation affects their regulation of trophoblast behaviour[J].Placenta,2016,47:73-80.
[25]Chaiworapongsa T,Chaemsaithong P,Yeo L,et al.Pre-eclampsia part 1:current understanding of its pathophysiology[J].Nat Rev Nephrol,2014,10(8):466-480.
[26]Faas MM,Spaans F,De Vos P.Monocytes and macrophages in pregnancy and pre-eclampsia[J].Front Immunol,2014,5:298.
[27]Svensson-Arvelund J,Ernerudh J,Buse E,et al.The placenta in toxicology.Part II:Systemic and local immune adaptations in pregnancy[J].Toxicol Pathol,2014,42(2):327-338.
[28]Milosevic-Stevanovic J,Krstic M,Radovic-Janosevic D,et al.Number of decidual natural killer cells¯ophages in preeclampsia[J].Indian J Med Res,2016,144(6):823-830.
[29]Reister F,Frank HG,Heyl W,et al.The distribution of macrophages in spiral arteries of the placental bed in pre-eclampsia differs from that in healthy patients[J].Placenta,1999,20(2/3):229-233.
[30]Cotechini T,Komisarenko M,Sperou A,et al.Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia[J].J Exp Med,2014,211(1):165-179.
[31]Jin LP,Fan DX,Li DJ.Regulation of costimulatory signal in maternal-fetal immune tolerance[J].Am J Reprod Immunol,2011,66(2):76-83.
[32]杜涛,黄海,刘玉昆,等.不明原因复发性流产与蜕膜组织中巨噬细胞自噬状态之间关系探讨[J].中国实用妇科与产科杂志,2015,31(8):763-767..
[33]Xu Y,Romero R,Miller D,et al.An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment[J].J Immunol,2016,196(6):2476-2491.
[34]Li XL,Wei HX,Zhang H,et al.A meta analysis on risks of adverse pregnancy outcomes in Toxoplasma gondii infection[J].PLoS One,2014,9(5):e97775.
[35]Shynlova O,Nedd-Roderique T,Li Y,et al.Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling[J].J Cell Mol Med,2013,17(2):311-324.
[36]Li Z,Zhao M,Li T,et al.Decidual Macrophage Functional Polarization during Abnormal Pregnancy due to Toxoplasma gondii:Role for LILRB4[J].Front Immunol,2017,8:1013.
[37]Matsumoto Y,Wang LL,Yokoyama WM,et al.Uterine macrophages express the gp49B inhibitory receptor in midgestation[J].J Immunol,2001,166(2):781-786.
[2]Bulmer JN,Williams PJ,Lash GE.Immune cells in the placental bed[J].Int J Dev Biol,2010,54(2/3):281-294.
[3]Care AS,Diener KR,Jasper MJ,et al.Macrophages regulate corpus luteum development during embryo implantation in mice[J].J Clin Invest,2013,123(8):3472-3487.
[4]Mor G,Cardenas I,Abrahams V,et al.Inflammation and pregnancy:the role of the immune system at the implantation site[J].Ann NYAcad Sci,2011,1221:80-87.
[5]Aldo PB,Racicot K,Craviero V,et al.Trophoblast induces monocyte differentiation into CD14+/CD16+macrophages[J].Am J Reprod Immunol,2014,72(3):270-284.
[6]Houser BL.Decidual macrophages and their roles at the maternalfetal interface[J].Yale J Biol Med,2012,85(1):105-118.
[7]Martinez FO,Helming L,Gordon S.Alternative activation of macrophages:an immunologic functional perspective[J].Annu Rev Immunol,2009,27:451-483.
[8]Renaud SJ,Graham CH.The role of macrophages in utero-placental interactions during normal and pathological pregnancy[J].Immunol Invest,2008,37(5):535-564.
[9]Mantovani A,Sica A,Sozzani S,et al.The chemokine system in diverse forms of macrophage activation and polarization[J].Trends Immunol,2004,25(12):677-686.
[10]Martinez FO,Gordon S,Locati M,et al.Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization:new molecules and patterns of gene expression[J].J Immunol,2006,177(10):7303-7311.
[11]Brown MB,von Chamier M,Allam AB,et al.M1/M2 macrophage polarity in normal and complicated pregnancy[J].Front Immunol,2014,5:606.
[12]Italiani P,Boraschi D.From Monocytes to M1/M2 Macrophages:Phenotypical vs.Functional Differentiation[J].Front Immunol,2014,5:514.
[13]Kong L,Zhang Q,Chao J,et al.Polarization of macrophages induced by Toxoplasma gondii and its impact on abnormal pregnancy in rats[J].Acta Trop,2015,143:1-7.
[14]Vomhof-DeKrey E,Darland D,Ghribi O,et al.Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFαexpression in Sprague-Dawley rats[J].JReprod Immunol,2016,118:9-17.
[15]Lash GE,Pitman H,Morgan HL,et al.Decidual macrophages:key regulators of vascular remodeling in human pregnancy[J].J Leukoc Biol,2016,100(2):315-325.
[16]Fu B,Wei H.Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface[J].Sci China Life Sci,2016,59(12):1224-1231.
[17]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.
[18]Krausgruber T,Blazek K,Smallie T,et al.IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses[J].Nat Immunol,2011,12(3):231-238.
[19]Svensson J,Jenmalm MC,Matussek A,et al.Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10[J].J Immunol,2011,187(7):3671-3682.
[20]Svensson-Arvelund J,Mehta RB,Lindau R,et al.The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages[J].JImmunol,2015,194(4):1534-1544.
[21]Smith SD,Dunk CE,Aplin JD,et al.Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy[J].Am J Pathol,2009,174(5):1959-1971.
[22]高瑞花,陈雷宁,谭雯雅,等.围着床期小鼠子宫中巨噬细胞的变化及作用[J].南方医科大学学报,2015,35(3):365-369.
[23]Toda N,Toda H,Okamura T.Regulation of myometrial circulation and uterine vascular tone by constitutive nitric oxide[J].Eur JPharmacol,2013,714(1/2/3):414-423.
[24]Buckley RJ,Whitley GS,Dumitriu IE,et al.Macrophage polarisation affects their regulation of trophoblast behaviour[J].Placenta,2016,47:73-80.
[25]Chaiworapongsa T,Chaemsaithong P,Yeo L,et al.Pre-eclampsia part 1:current understanding of its pathophysiology[J].Nat Rev Nephrol,2014,10(8):466-480.
[26]Faas MM,Spaans F,De Vos P.Monocytes and macrophages in pregnancy and pre-eclampsia[J].Front Immunol,2014,5:298.
[27]Svensson-Arvelund J,Ernerudh J,Buse E,et al.The placenta in toxicology.Part II:Systemic and local immune adaptations in pregnancy[J].Toxicol Pathol,2014,42(2):327-338.
[28]Milosevic-Stevanovic J,Krstic M,Radovic-Janosevic D,et al.Number of decidual natural killer cells¯ophages in preeclampsia[J].Indian J Med Res,2016,144(6):823-830.
[29]Reister F,Frank HG,Heyl W,et al.The distribution of macrophages in spiral arteries of the placental bed in pre-eclampsia differs from that in healthy patients[J].Placenta,1999,20(2/3):229-233.
[30]Cotechini T,Komisarenko M,Sperou A,et al.Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia[J].J Exp Med,2014,211(1):165-179.
[31]Jin LP,Fan DX,Li DJ.Regulation of costimulatory signal in maternal-fetal immune tolerance[J].Am J Reprod Immunol,2011,66(2):76-83.
[32]杜涛,黄海,刘玉昆,等.不明原因复发性流产与蜕膜组织中巨噬细胞自噬状态之间关系探讨[J].中国实用妇科与产科杂志,2015,31(8):763-767..
[33]Xu Y,Romero R,Miller D,et al.An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment[J].J Immunol,2016,196(6):2476-2491.
[34]Li XL,Wei HX,Zhang H,et al.A meta analysis on risks of adverse pregnancy outcomes in Toxoplasma gondii infection[J].PLoS One,2014,9(5):e97775.
[35]Shynlova O,Nedd-Roderique T,Li Y,et al.Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling[J].J Cell Mol Med,2013,17(2):311-324.
[36]Li Z,Zhao M,Li T,et al.Decidual Macrophage Functional Polarization during Abnormal Pregnancy due to Toxoplasma gondii:Role for LILRB4[J].Front Immunol,2017,8:1013.
[37]Matsumoto Y,Wang LL,Yokoyama WM,et al.Uterine macrophages express the gp49B inhibitory receptor in midgestation[J].J Immunol,2001,166(2):781-786.