滋养层细胞表达的趋化因子（C-C 基元）配体 25 及其受体 Ccr9 表达的白细胞：胚胎植入期间的联盟？

Chemokine (C-C motif) ligand 25 expressed by trophoblast cells and leukocytes bearing its receptor Ccr9: An alliance during embryo implantation?

机构信息

Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Department of Obstetrics and Gynecology, Laboratory of Medical Investigation, School of Medicine, University of São Paulo, São Paulo, Brazil.

出版信息

Am J Reprod Immunol. 2018 Jan;79(1). doi: 10.1111/aji.12783. Epub 2017 Nov 20.

DOI:10.1111/aji.12783

PMID:29154408

Abstract

PROBLEM

We hypothesized that trophoblast expression of Ccl25 attracts a specific leukocyte cell population to the implantation site for local regulation.

METHOD OF STUDY

Mice blastocysts, ectoplacental cones, and decidua at gestational days 3.5-7.5 were evaluated for Ccl25 and Ccr9 expressions. Peripheral availability and characterization of Ccr9+ leukocytes were determined by flow cytometry. Leukocyte chemotaxis was assessed in the presence of Ccl25 recombinant protein and embryos using antisense oligomers (ODNs) to Ccl25 and Ccr9 neutralizing antibody.

RESULTS

Ccl25 was expressed by embryonic cells, whereas Ccr9 expression was strong at the maternal compartment and in PBMC. Immunolocalization confirmed this expression. In vitro, chemotaxis assays showed that the embryonic Ccl25 signals to Ccr9+ PBMCs. Maternal Ccr9+α4β7+ monocytes switch from an anti-inflammatory phenotype (F4/80+11b+Ly6C-TGF-β+ cells, pre-implantation) to an inflammatory profile (F4/80+11b+Ly6C+TNF-α+ cells, post-implantation).

CONCLUSION

Our data support the establishment of a CCL25/CCR9-axis at the maternal-fetal interface in mice, which may be involved in immune regulatory mechanisms during embryo implantation.

摘要

问题

我们假设滋养层细胞表达的 Ccl25 吸引特定的白细胞亚群到着床部位进行局部调节。

方法

评估了妊娠第 3.5-7.5 天的小鼠胚泡、胎盘外 cones 和蜕膜中的 Ccl25 和 Ccr9 表达情况。通过流式细胞术确定外周 Ccr9+白细胞的可用性和特征。使用针对 Ccl25 和 Ccr9 的反义寡核苷酸 (ODN) 和中和抗体评估 Ccl25 重组蛋白和胚胎对白细胞趋化性的影响。

结果

Ccl25 由胚胎细胞表达，而 Ccr9 表达在母体部位和 PBMC 中较强。免疫定位证实了这种表达。在体外，趋化性测定表明胚胎 Ccl25 信号可传递给 Ccr9+PBMC。母体 Ccr9+α4β7+单核细胞从抗炎表型（F4/80+11b+Ly6C-TGF-β+细胞，着床前）转变为炎症表型（F4/80+11b+Ly6C+TNF-α+细胞，着床后）。