摘要
Background:Interleukin 35(IL-35) belongs to the IL-12 cytokine family that inhibits T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells(i Tr35).Physiological pregnancy requires balence of maternal–fetal tolerance where trophoblasts play essential roles.Objective:We sought to identify the function of IL-35 secreted by trophoblasts in maintain maternal-fetal tolerance during pregnancy.Methods:Human primary trophoblast cells and human trophoblast cell lines,HTR-8/SVneo,were used for ex vivo studies.Human CD4+CD25-T cells isolated from PBMC were cultured with supernatant of primary trophoblast cells or HTR-8/SVneo.ELISA assay and immunocytochemistry was used identify IL-35 level of trophoblast cells.Expression of p35 and EBI3 was quantified using flow cytometry and real-time RT-PCR.Molecules in JAK-STAT pathway were evaluated by western blot method.Results:In this study we showed that first-trimester human trophoblast cells expressed and secreted IL-35.The supernatants from trophoblast cells inhibited directly the proliferation of CD4+ effective T cells(Teffs) by IL-35-dependent manner.Like exogenous IL-35,trophoblasts-drived IL-35 also induced Teffs into i Tr35 with increased expression of p35 and EBI3 at both m RNA and protein levels.Furthermore,we demonstrated that trophoblasts-drived IL-35 played the inhibition function by activating transcription factor STAT1/STAT3.Conclusions:Human trophoblasts contribute to maternal-fetal tolerance by converting the suppressed decidual T cells into i Tr35 via the secretion of IL-35 in human early pregnancy.
Background:Interleukin 35(IL-35) belongs to the IL-12 cytokine family that inhibits T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells(i Tr35).Physiological pregnancy requires balence of maternal–fetal tolerance where trophoblasts play essential roles.Objective:We sought to identify the function of IL-35 secreted by trophoblasts in maintain maternal-fetal tolerance during pregnancy.Methods:Human primary trophoblast cells and human trophoblast cell lines,HTR-8/SVneo,were used for ex vivo studies.Human CD4+CD25-T cells isolated from PBMC were cultured with supernatant of primary trophoblast cells or HTR-8/SVneo.ELISA assay and immunocytochemistry was used identify IL-35 level of trophoblast cells.Expression of p35 and EBI3 was quantified using flow cytometry and real-time RT-PCR.Molecules in JAK-STAT pathway were evaluated by western blot method.Results:In this study we showed that first-trimester human trophoblast cells expressed and secreted IL-35.The supernatants from trophoblast cells inhibited directly the proliferation of CD4+ effective T cells(Teffs) by IL-35-dependent manner.Like exogenous IL-35,trophoblasts-drived IL-35 also induced Teffs into i Tr35 with increased expression of p35 and EBI3 at both m RNA and protein levels.Furthermore,we demonstrated that trophoblasts-drived IL-35 played the inhibition function by activating transcription factor STAT1/STAT3.Conclusions:Human trophoblasts contribute to maternal-fetal tolerance by converting the suppressed decidual T cells into i Tr35 via the secretion of IL-35 in human early pregnancy.
引文