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羊水糖蛋白作为巨噬细胞半乳糖型C型凝集素的潜在配体及其在孕期免疫调节中的可能意义。

Amniotic fluid glycoproteins as potential ligands for macrophage galactose-type C-type lectin and their possible implications for immunoregulation during pregnancy.

作者信息

Szczykutowicz Justyna, Zimmer Mariusz, Orczyk-Pawiłowicz Magdalena

机构信息

Division of Chemistry and Immunochemistry, Department of Biochemistry and Immunochemistry, Wroclaw Medical University, M. Skłodowskiej-Curie 48/50, 50-369, Wroclaw, Poland.

Clinical Department of Obstetrics and Gynecology, University Centre of Obstetrics and Gynecology, Wroclaw Medical University, Wroclaw, Poland.

出版信息

Sci Rep. 2025 Sep 26;15(1):32966. doi: 10.1038/s41598-025-16909-2.

DOI:10.1038/s41598-025-16909-2
PMID:41006428
Abstract

Immunity during pregnancy must be precisely balanced, because the mother's body needs to effectively fight pathogens while maintaining tolerance of the semi-allogeneic fetus. Factors that participate in achieving the proper immune balance during pregnancy include glycoproteins that expose sugar residues recognized by specific lectin receptors. Several types of lectins and their ligands have been detected at the maternal-fetal interface, and changes in their expression levels have been correlated with pregnancy complications. Although the presence of potential sugar ligands for human macrophage galactose-type lectin (MGL), including LacdiNAc and (sialo)Tn antigen, has been detected in amniotic fluid, placenta and fetal tissues, the interaction between them and its possible role have not been elucidated so far. The aims of the present study were to evaluate reactivity of MGL with amniotic fluid proteins and to identify and characterize the amniotic ligands of MGL. The analysis proved the ability of MGL to interact with amniotic glycoproteins and revealed the potential protein carriers of glycans recognized by MGL, including mucins, mucin-like proteins, and uromodulin. Bioinformatics analysis assigned the identified glycoproteins as being involved in immune processes such as regulation of signaling pathways activated in the response to Toll-like receptor (TLR) agonist stimulation or modulation of antimicrobial responses. Our research suggests that MGL-mediated interactions may be involved in maintaining the delicate immune balance during pregnancy. Our results may be helpful in future implementation of modern therapies based on the glycan ligands of MGL in the context of avoiding miscarriages and preterm birth.

摘要

孕期的免疫必须精确平衡,因为母体需要在有效对抗病原体的同时维持对半同种异体胎儿的耐受性。孕期参与实现适当免疫平衡的因素包括暴露特定凝集素受体可识别糖残基的糖蛋白。在母胎界面已检测到几种类型的凝集素及其配体,它们表达水平的变化与妊娠并发症相关。尽管在羊水、胎盘和胎儿组织中已检测到人类巨噬细胞半乳糖型凝集素(MGL)潜在的糖配体,包括乳糖胺和(唾液酸)Tn抗原,但它们之间的相互作用及其可能的作用迄今尚未阐明。本研究的目的是评估MGL与羊水蛋白的反应性,并鉴定和表征MGL的羊水配体。分析证明了MGL与羊水糖蛋白相互作用的能力,并揭示了MGL识别的聚糖潜在的蛋白质载体,包括粘蛋白、粘蛋白样蛋白和尿调节蛋白。生物信息学分析将鉴定出的糖蛋白归类为参与免疫过程,如对Toll样受体(TLR)激动剂刺激的反应中激活的信号通路调节或抗菌反应的调节。我们的研究表明,MGL介导的相互作用可能参与维持孕期微妙的免疫平衡。我们的结果可能有助于未来在避免流产和早产的背景下基于MGL糖配体的现代疗法的实施。

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