Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System

Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用

基本信息

项目摘要

ABSTRACT The importance of placental and decidual secreted factors as mediators of the immunological adjustments needed to accommodate the genetically different mother and fetus during hemochorial pregnancies is well recognized. Galectins are a family of lectins with intracellular and extracellular functions. Secreted galectins bind to N-acetyllactosamine (LacNAc) and form lattices between glycoproteins on the surface of cells and between cells, promoting a plethora of biological activities including regulation of the adaptive and innate immune response. Members of the galectin family exhibit notable differences in carbohydrate specificity and affinity resulting in different functions. Recently, Galectin-9 (Gal-9), which is expressed at the maternal fetal- interface, has been suggested to play a role in maternal T-cell tolerance by binding to its receptors which include among others T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and CD44. On the other hand, Gal-9 has been reported to induce the secretion of pro-inflammatory cytokines by myeloid cells. Recently, we found that Pregnancy-specific glycoprotein 1(PSG1), which is secreted by placental trophoblasts at increasing concentration as pregnancy progresses, binds to Gal-9. PSG1 binds to Gal-9 with high affinity and the interaction is glycan-mediated. Importantly, the concentration of PSG1 is lower than normal in some pregnancy complications including pre-eclampsia. Activation of the innate immune system has been proposed to contribute to trophoblast invasion in the early decidua and to parturition, however it is also associated with adverse pregnancy outcomes when it occurs in the second and third trimesters. Therefore, the temporal and spatial aspects of reducing inflammation during pregnancy represent a complex and essential process for pregnancy success. We propose that the newly found interaction between Gal-9 and PSG1 contributes to the qualitative differences in the immune response required for pregnancy success and that besides their previously identified individual functions, the interplay between these two proteins plays an important role in the modulation of immune cells. Therefore we propose to carry out the following Specific Aims: (1) Analyze the binding of native and recombinant PSG1 to the N-terminal and C-terminal carbohydrate recognition domains of Gal-9. (2) Determine the individual and combined effects of PSG1 and Gal-9 or the individual Gal-9 CRDs on the phenotype and secretion of cytokines by monocytes and decidual macrophages. (3) Determine the effect of individual and combined treatment of PSG1 and Gal-9 in human CD4+ T-cell apoptosis and frequency of CD4+ FoxP3+ T-regulatory cells.
抽象的 胎盘和蜕膜分泌因子作为免疫介质的重要性 需要进行调整以适应基因不同的母亲和胎儿 血绒妊娠已得到广泛认可。半乳糖凝集素是一类具有细胞内和 细胞外功能。分泌的半乳糖凝集素与 N-乙酰基乳糖胺 (LacNAc) 结合并形成晶格 细胞表面和细胞之间的糖蛋白之间,促进大量的 生物活性,包括适应性和先天免疫反应的调节。会员 半乳糖凝集素家族的碳水化合物特异性和亲和力表现出显着差异 在不同的功能中。最近,半乳糖凝集素 9 (Gal-9) 在母胎中表达, 界面,已被认为通过与其受体结合在母体 T 细胞耐受中发挥作用 其中包括 T 细胞免疫球蛋白和 mucin-domain contains-3 (Tim-3) 和 CD44。另一方面,Gal-9 据报道可诱导促炎物质的分泌。 骨髓细胞产生的细胞因子。最近,我们发现妊娠特异性糖蛋白1(PSG1), 随着妊娠的进展,胎盘滋养层分泌的浓度不断增加, 与 Gal-9 结合。 PSG1 以高亲和力与 Gal-9 结合,并且相互作用是聚糖介导的。 重要的是,在某些妊娠并发症中 PSG1 的浓度低于正常值 包括先兆子痫。 已提出先天免疫系统的激活有助于滋养层 侵入早期蜕膜并导致分娩,但它也与不良反应有关 妊娠中期和晚期的妊娠结局。因此,时间 减少怀孕期间炎症的空间和空间方面代表了一个复杂而重要的问题 怀孕成功的过程。我们提出新发现的 Gal-9 和 PSG1 导致妊娠所需免疫反应的质的差异 成功,除了之前确定的各自功能之外,之间的相互作用 这两种蛋白质在免疫细胞的调节中发挥着重要作用。因此我们 建议实现以下具体目标:(1)分析天然和重组体的结合 PSG1 连接到 Gal-9 的 N 端和 C 端碳水化合物识别域。 (2)确定 PSG1 和 Gal-9 或单个 Gal-9 CRD 对 单核细胞和蜕膜巨噬细胞的表型和细胞因子分泌。 (3)确定 PSG1 和 Gal-9 单独和联合治疗对人 CD4+ T 细胞的影响 CD4+ FoxP3+ T 调节细胞的凋亡和频率。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Medawar's PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation.
  • DOI:
    10.3389/fimmu.2021.784473
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
    Menkhorst E;Than NG;Jeschke U;Barrientos G;Szereday L;Dveksler G;Blois SM
  • 通讯作者:
    Blois SM
Kathryn V. Holmes: A Career of Contributions to the Coronavirus Field.
  • DOI:
    10.3390/v14071573
  • 发表时间:
    2022-07-20
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
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Gabriela S Dveksler其他文献

Gabriela S Dveksler的其他文献

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{{ truncateString('Gabriela S Dveksler', 18)}}的其他基金

Not all members of the pregnancy-specific glycoprotein family are created equal
妊娠特异性糖蛋白家族的所有成员并非生而平等
  • 批准号:
    10349979
  • 财政年份:
    2022
  • 资助金额:
    $ 22.87万
  • 项目类别:
Not all members of the pregnancy-specific glycoprotein family are created equal
妊娠特异性糖蛋白家族的所有成员并非生而平等
  • 批准号:
    10615689
  • 财政年份:
    2022
  • 资助金额:
    $ 22.87万
  • 项目类别:
Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System
Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用
  • 批准号:
    10302501
  • 财政年份:
    2021
  • 资助金额:
    $ 22.87万
  • 项目类别:
Therapeutic potential of PSG1 administration in GVHD
PSG1 给药在 GVHD 中的治疗潜力
  • 批准号:
    9111289
  • 财政年份:
    2016
  • 资助金额:
    $ 22.87万
  • 项目类别:
Pregnancy specific glycoprotein 1 activates transforming growth factor beta
妊娠特异性糖蛋白 1 激活转化生长因子 β
  • 批准号:
    8533727
  • 财政年份:
    2012
  • 资助金额:
    $ 22.87万
  • 项目类别:
Pregnancy specific glycoprotein 1 activates transforming growth factor beta
妊娠特异性糖蛋白 1 激活转化生长因子 β
  • 批准号:
    8359204
  • 财政年份:
    2012
  • 资助金额:
    $ 22.87万
  • 项目类别:
Immunomodulation by Pregnancy Specific Glycoprotein 17
妊娠特异性糖蛋白 17 的免疫调节
  • 批准号:
    6823250
  • 财政年份:
    2002
  • 资助金额:
    $ 22.87万
  • 项目类别:
Immunomodulation by Pregnancy Specific Glycoprotein 17
妊娠特异性糖蛋白 17 的免疫调节
  • 批准号:
    6688455
  • 财政年份:
    2002
  • 资助金额:
    $ 22.87万
  • 项目类别:
Immunomodulation by Pregnancy Specific Glycoprotein 17
妊娠特异性糖蛋白 17 的免疫调节
  • 批准号:
    6580154
  • 财政年份:
    2002
  • 资助金额:
    $ 22.87万
  • 项目类别:
Immunomodulation by Pregnancy Specific Glycoprotein 17
妊娠特异性糖蛋白 17 的免疫调节
  • 批准号:
    6982814
  • 财政年份:
    2002
  • 资助金额:
    $ 22.87万
  • 项目类别:

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