The atypical chemokine receptor D6 is expressed by trophoblasts and plays roles in placental formation and chemokine scavenging

Fiona Menzies, P.J. Teoh, C. Waddell, S.M. Nelson, R.J.B. Nibbs

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Placental dysfunction contributes to many important obstetric problems, including preeclampsia and fetal growth restriction. The crosstalk between maternal and fetal cells is critically important for effective placental function. Chemokines have been implicated in both the regulation of trophoblast migration into the uterus, and the recruitment of maternal immune cells into gestational tissues. The focus of this study is the atypical chemokine receptor D6, which has been hypothesized to be involved in reducing inflammation at the fetomaternal interface. Chemokine receptor expression by primary human trophoblasts did not vary with length of time in culture, however D6 mRNA was more abundant than other receptors (CCR1, CCR2, CCR3, CCR5, CCRL1, CXCR4) examined. To confirm expression of D6 protein in these cells, Western blotting and immunofluorescent staining were performed. The ability of trophoblasts to internalise CCL2 from the culture medium was found to be D6-dependent, thus demonstrating the chemokine scavenging ability of D6. D6-deficient mice exhibit higher rates of stillbirth and neonatal death than their wild-type counterparts (stillbirth, KO 21.3%, WT 10.2%; neonatal death, KO 37.0%, WT 16.7%, both p<0.0001). Placental stereology revealed that at E14 of gestation, D6-deficient mice have a larger junctional zone than wild type mice, and a smaller labyrinthine zone. However, by E18 of gestation, these differences are diminished. This is the first study to examine D6 in primary human cells, demonstrating a role for this receptor in immune regulation at the fetomaternal interface. In addition, our animal studies also suggest a role for D6 in regulating placenta formation.
Original languageEnglish
Publication statusPublished - Aug 2013
Event15th International Congress of Immunology (ICI) - Milan, Italy
Duration: 22 Aug 201328 Aug 2013

Conference

Conference15th International Congress of Immunology (ICI)
CountryItaly
CityMilan
Period22/08/1328/08/13

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