Expression of Interleukin-27 by Human Trophoblast Cells

• Published in: Placenta (Eastbourne) 2007-11, Vol.28 (11), p.1133-1140
• Main Authors: Coulomb-L'Herminé, A, Larousserie, F, Pflanz, S, Bardel, E, Kastelein, R.A, Devergne, O
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Western; Cells, Cultured; Cytokine; Embryology: invertebrates and vertebrates. Teratology; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - immunology; Gestational Age; Humans; Immunohistochemistry; Immunoregulation; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-27; Interleukins - genetics; Interleukins - metabolism; Internal Medicine; Minor Histocompatibility Antigens; Obstetrics and Gynecology; Placenta - immunology; Pregnancy; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; Trophoblast; Trophoblasts - cytology; Trophoblasts - immunology
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2007.06.004

Abstract Cytokines produced at the fetal–maternal interface play a key role in regulating maternal tolerance to the fetus and successful pregnancy. Previously, we showed that EBV-induced gene 3 (EBI3), an interleukin (IL)-12 p40 homologue, was expressed at very high levels by syncytiotrophoblasts and extravillous trophoblasts throughout human pregnancy. EBI3 was recently shown to associate with a novel ligand, p28, to form a new heterodimeric cytokine with important immunoregulatory functions, IL-27. In this study, we investigated whether EBI3 expression by trophoblast cells is associated with that of p28 to form IL-27. We found that genes encoding IL-27 (EBI3 and p28) and its receptor (IL-27R and gp130) were expressed in the placenta at various stages of pregnancy. Co-immunoprecipitation experiments performed from placental lysates, and ELISA of culture supernatants from placental explants, showed that IL-27 heterodimer was produced and released from placental cells. In situ studies of placentae of first, second and third trimester of pregnancy, and of choriocarcinomas, demonstrated that syncytiotrophoblast cells co-expressed EBI3 and p28. Similarly, extravillous trophoblast cells invading the decidua were found to co-express both subunits of IL-27. These data suggest that IL-27 may be part of the cytokine network regulating local immune responses and angiogenesis during human pregnancy.