Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy ...Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not beencompletely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in themaintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces thepolarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, whichfacilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown inthe present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involvedin decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic andimmune-tolerant milieu required for successful fetal development.展开更多
The regulatory mechanism of Th2 bias at the maternal/fetal interface remains unclear. In this study, we characterized cytokine production in decidual stromal cells （DSCs）, decidual immune cells （DICs） and embryo-d...The regulatory mechanism of Th2 bias at the maternal/fetal interface remains unclear. In this study, we characterized cytokine production in decidual stromal cells （DSCs）, decidual immune cells （DICs） and embryo-derived trophoblast cells, and investigated the regulation of CXCL12/CXCR4 interaction on Th2 bias at the maternal/fetal interface in early human pregnancy. We found differential production of Th 1-type and Th2-type cytoki nes by trophoblasts, DSCs and DICs. The secretion of these cytokines varied in different cell cocultures, conduced to Th2 bias. Flow cytometry showed that coculture of trophoblasts with DSCs and DICs significantly increased IL-4 and IL-IO production in trophoblasts, and IL-IO production in DSCs. However, the coculture of trophoblasts with DSCs and DICs significantly increased interferon （IFN）-7 expression in DSCs, and tumor-necrosis factor （TNF）-a expression in DICs. No change was seen in Thl-type cytokine production in trophoblasts, and in Th2-type cytokine production in DICs in all cocultures. Furthermore, pre-treatment with anti-CXCR4 neutralizing antibody upregulated the production of the Thl-type cytokines IFN-y and TNF-a, and downregulated the production of the Th2-type cytokines IL-4 and IL-IO, in trophoblasts, DSCs, DICs or their cocultures. Interestingly, rhCXCL12 inhibited production of the Thl-type cytokine TNF-a and enhanced the expression of the Th2-type cytokines such as IL-4 and IL-IO in DICs; this effect was abrogated by anti-CXCR4 antibody. Our present study has elucidated the individual contributions of component cells to the shaping of Th2 bias, and uncovered a complicated cross-talk viathe CXCL12/CXCR4 signal at the maternal/fetal interface in early human pregnancy.展开更多
Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early preg...Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3-CD56^brightCD25^＋ phenotype. We found that CD56^brightCD25^＋ NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25^＋ dNK cells account for approximately 75% of CD25-expressing decidual immune cells （DICs）. However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25^＋ NK cells. Furthermore, CD25^＋ and CD25^- dNK cells exhibit distinct phenotypes： CD25^＋ dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK （pNK） cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25^＋ dNK cells and contributes to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells, which exert a regulating effect at the maternal/fetal interface.展开更多
Objective:To investigate the roles of COX-2,TNF-α,IL-6 in the pathogenesis of autoimmunetype recurrent spontaneous abortion(RSA).Methods:RT-PCR was used to detect the mRNA of COX-2,TNF-α.IL-6 in the trophoblast cell...Objective:To investigate the roles of COX-2,TNF-α,IL-6 in the pathogenesis of autoimmunetype recurrent spontaneous abortion(RSA).Methods:RT-PCR was used to detect the mRNA of COX-2,TNF-α.IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The COX-2,TNF-α.IL-6 protein expressions were determined by using immunohistochemisry staining method.The COX-2,TNF-α,IL-6 protein expressions were determined by ELISA.Results:The embryo loss rates in experiment group was significantly higher than that in normal pregnancy control group,the expression of COX-2,TNF-α,IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The expression of COX-2 in autoimmunetype recurrent spontaneous abortion was significantly lesser than in normal pregnant models.The expression of TNF-α,IL-6 in autoimmune-type recurrent spontaneous abortion was significantly higher than in normal pregnant models.There was a positively correlation between TNF-αand IL-6.There was no relationship between COX-2,TNF-αand IL-6.Conclusions:The abnormal expression of COX-2,TNF-αand IL-6 may result in RSA.展开更多
基金This study was funded by grant number MOST 2015CB943300 awarded to Da-Jin Lia grant from the National Natural Science Foundation of China,number 81200425,awarded to Xiao-Qiu Wang+2 种基金a grant from the National Natural Science Foundation of China,number 81471548,awarded to D.-J.L.a grant from the National Natural Science Foundation of China,number 81571512,awarded to Q.F.a grant from The Department of Science and Technology in Shandong Province,number ZR2015JL027,awarded to Q.F.
文摘Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not beencompletely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in themaintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces thepolarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, whichfacilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown inthe present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involvedin decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic andimmune-tolerant milieu required for successful fetal development.
文摘The regulatory mechanism of Th2 bias at the maternal/fetal interface remains unclear. In this study, we characterized cytokine production in decidual stromal cells （DSCs）, decidual immune cells （DICs） and embryo-derived trophoblast cells, and investigated the regulation of CXCL12/CXCR4 interaction on Th2 bias at the maternal/fetal interface in early human pregnancy. We found differential production of Th 1-type and Th2-type cytoki nes by trophoblasts, DSCs and DICs. The secretion of these cytokines varied in different cell cocultures, conduced to Th2 bias. Flow cytometry showed that coculture of trophoblasts with DSCs and DICs significantly increased IL-4 and IL-IO production in trophoblasts, and IL-IO production in DSCs. However, the coculture of trophoblasts with DSCs and DICs significantly increased interferon （IFN）-7 expression in DSCs, and tumor-necrosis factor （TNF）-a expression in DICs. No change was seen in Thl-type cytokine production in trophoblasts, and in Th2-type cytokine production in DICs in all cocultures. Furthermore, pre-treatment with anti-CXCR4 neutralizing antibody upregulated the production of the Thl-type cytokines IFN-y and TNF-a, and downregulated the production of the Th2-type cytokines IL-4 and IL-IO, in trophoblasts, DSCs, DICs or their cocultures. Interestingly, rhCXCL12 inhibited production of the Thl-type cytokine TNF-a and enhanced the expression of the Th2-type cytokines such as IL-4 and IL-IO in DICs; this effect was abrogated by anti-CXCR4 antibody. Our present study has elucidated the individual contributions of component cells to the shaping of Th2 bias, and uncovered a complicated cross-talk viathe CXCL12/CXCR4 signal at the maternal/fetal interface in early human pregnancy.
基金This work was supported by the Key Project of Shanghai Basic Research from Shanghai Municipal Science and Technology Commission （STCSM） （12JC1401600 to DJL）, the Key Project of Shanghai Municipal Education Commission （MECSM） （14ZZ013 to MRD） and the Nature Science Foundation from National Nature Science Foundation of China （NSFC） （NSFC31270969 to DJL NSFC81070537, NSFC31171437 and NSFC81370770 to MRD+1 种基金 NSFC31300751 to HLP NSFC81370730 to QF）.
文摘Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3-CD56^brightCD25^＋ phenotype. We found that CD56^brightCD25^＋ NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25^＋ dNK cells account for approximately 75% of CD25-expressing decidual immune cells （DICs）. However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25^＋ NK cells. Furthermore, CD25^＋ and CD25^- dNK cells exhibit distinct phenotypes： CD25^＋ dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK （pNK） cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25^＋ dNK cells and contributes to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells, which exert a regulating effect at the maternal/fetal interface.
基金supported by the National Key Research and Development Project,China(No.2018YFC1002802,2017YFC1001404)Huxiang Talent Project of Hunan Provincial Science and Technology Department,China(No.2018RS3030)。
文摘Objective:To investigate the roles of COX-2,TNF-α,IL-6 in the pathogenesis of autoimmunetype recurrent spontaneous abortion(RSA).Methods:RT-PCR was used to detect the mRNA of COX-2,TNF-α.IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The COX-2,TNF-α.IL-6 protein expressions were determined by using immunohistochemisry staining method.The COX-2,TNF-α,IL-6 protein expressions were determined by ELISA.Results:The embryo loss rates in experiment group was significantly higher than that in normal pregnancy control group,the expression of COX-2,TNF-α,IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The expression of COX-2 in autoimmunetype recurrent spontaneous abortion was significantly lesser than in normal pregnant models.The expression of TNF-α,IL-6 in autoimmune-type recurrent spontaneous abortion was significantly higher than in normal pregnant models.There was a positively correlation between TNF-αand IL-6.There was no relationship between COX-2,TNF-αand IL-6.Conclusions:The abnormal expression of COX-2,TNF-αand IL-6 may result in RSA.
