title: Human placental trophoblasts express the immunosuppressive cytokine IL-35.
abstract: Studies of maternal-fetal tolerance focus on defining mechanisms for establishment of immunological privilege within the uterus during pregnancy. Fetal trophoblasts play a key role in maternal tolerance, in part through cytokines production. As a novel inhibitory cytokine, IL-35 is produced by Foxp3(+) regulatory T cells (Tregs) and mediates maximal suppression of Tregs. The purpose of the study is to analyze the expression of IL-35 in first-trimester human placental trophoblasts. IL-35 expression was detected at both protein and mRNA levels by immunohistochemical staining and quantitative real-time PCR method, respectively and secretion of IL-35 was measured by ELISA assay. Our results demonstrated that human trophoblasts constitutively expressed IL-35. Ebi3 and p35 (two subunits of IL-35) mRNA was shown to be co-expressed in trophoblast cells. Moreover, large amounts of secreted IL-35 were detected in the supernatants of trophoblast cells. But we did not detect the constitutive expression of IL-35 in decidual stromal cells. Our findings confirmed for the first time that first-trimester human trophoblast cells expressed and secreted IL-35, which might contribute to their suppressive capacity to maternal immune cells. Therefore, IL-35 may be an important factor of the cytokine network regulating local immune responses during human pregnancy.
authors.affiliation: Institute of Basic Medical Sciences, Qi Lu Hospital, Shandong University, Jinan 250012, PR China. haitingmao@yahoo.com
authors.forename: Haiting
authors.initials: H
authors.lastname: Mao
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Song
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D021041:Placental Circulation / Q000276:immunology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D017154:Stromal Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology*
chemical_list: C097732:EBI3 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053765:Interleukin-12 Subunit p35; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; C532417:interleukin-35, human