Expression of interleukin-27 by human trophoblast cells.
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.
Service d'Anatomie Pathologique, Hôpital Antoine Béclère, Clamart, France.
A
A
Coulomb-L'Herminé
F
F
Larousserie
S
S
Pflanz
E
E
Bardel
R A
RA
Kastelein
O
O
Devergne
D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000276:immunology; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
C097732:EBI3 protein, human; C112441:IL27RA protein, human; D020381:Interleukin-17; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; D012313:RNA