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 disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)a...The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.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
妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是妊娠期特发性疾病,严重影响母婴健康,是孕产妇和围生儿死亡率升高的主要原因,但其确切病因及发病机制仍不清楚。近年发现,胎盘浅着床是HDP发病的重要机制,影响胎盘浅着床...妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是妊娠期特发性疾病,严重影响母婴健康,是孕产妇和围生儿死亡率升高的主要原因,但其确切病因及发病机制仍不清楚。近年发现,胎盘浅着床是HDP发病的重要机制,影响胎盘浅着床过程的因素可分为3个方面:一是影响滋养细胞侵袭能力,主要包括缺氧、细胞因子、表观遗传调控等;二是影响炎症因子浸润过程,包括趋化因子家族及蜕膜自然杀伤细胞等;三是影响细胞外基质降解的程度,主要包括基质金属蛋白酶(MMPs)及其相关的影响因素等。综述HDP胎盘浅着床的发生机制,以期为临床疾病早期诊断、治疗及预防提供一个新的方向。展开更多
Background： Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization （IVF） therapy, it is not yet clear which blastocyst morphological paralneters best...Background： Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization （IVF） therapy, it is not yet clear which blastocyst morphological paralneters best predict the outcomes of single blastocyst transfer. In addition. most of the previous studies did not exclude the effect of embryo aneuploidy on blastocysts transfer. Thus, the present study investigated the predictive value of various parameters on the pregnancy outcomes achieved via the transfer of frozcn euploid blastocysts. Methods： The study retrospectively analyzed 914 single euploid blastocyst transfer cycles that were performed at the Peking U laivcrsity Third Hospital Reproductive Medical Center between June 2011 and May 2016. The expansion, trophectoderm （TE）. and inner cell mass （ICM） quality of the blastocysts were assessed based on blastocyst parameters, and used to differentiate between ＂excellent＂, ＂good＂, ＂average＂, and ＂poor＂-quality embryos. The relationship between these embryo grades and the achieved pregnancy outcomes was then analyzed via the Chi-square and logistic regression tests. Results： For embryo grades of excellent, good, average and poor, the clinical pregnancy rates were 65.0%. 50.3%, 50.3% and 33.3%. respectively; and the live-birth rates were 50.0%, 49.7%, 42.3% and 25.0%, respectively. Both the clinical pregnancy ratc （x2= 21.28. P = 0.001） and live-birth rate （x2 = 13.50, P 〈 0.001） increased with the overall blastocyst grade. Both rates were significanlly higher after the transfer era blastocyst that exhibited either an A-grade or B-grade TE, and similarly, an A-grade ICM. than after the transfer el a blastocyst that exhibited a C-grade TE and/or ICM. The degree of blastocysl expansion had no apparent effect on the clinical pregnancy or live-birth rate. All odds ratio were adjusted for patient age, body mass index, length （years） of infertility history, and infertility type. Conclusions： A higher overall euploid blas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.
基金by the National Natural Science Foundation of China(81571462,81600353,and 81701472)Jiangsu Provincial Key Medical Center(YXZXB2016004)+1 种基金Jiangsu Biobank of Clinical Resources(BM2015004)Jiangsu Province Grant for Science and Technology(BK20161106).
文摘The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.
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.
文摘妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是妊娠期特发性疾病,严重影响母婴健康,是孕产妇和围生儿死亡率升高的主要原因,但其确切病因及发病机制仍不清楚。近年发现,胎盘浅着床是HDP发病的重要机制,影响胎盘浅着床过程的因素可分为3个方面:一是影响滋养细胞侵袭能力,主要包括缺氧、细胞因子、表观遗传调控等;二是影响炎症因子浸润过程,包括趋化因子家族及蜕膜自然杀伤细胞等;三是影响细胞外基质降解的程度,主要包括基质金属蛋白酶(MMPs)及其相关的影响因素等。综述HDP胎盘浅着床的发生机制,以期为临床疾病早期诊断、治疗及预防提供一个新的方向。
文摘Background： Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization （IVF） therapy, it is not yet clear which blastocyst morphological paralneters best predict the outcomes of single blastocyst transfer. In addition. most of the previous studies did not exclude the effect of embryo aneuploidy on blastocysts transfer. Thus, the present study investigated the predictive value of various parameters on the pregnancy outcomes achieved via the transfer of frozcn euploid blastocysts. Methods： The study retrospectively analyzed 914 single euploid blastocyst transfer cycles that were performed at the Peking U laivcrsity Third Hospital Reproductive Medical Center between June 2011 and May 2016. The expansion, trophectoderm （TE）. and inner cell mass （ICM） quality of the blastocysts were assessed based on blastocyst parameters, and used to differentiate between ＂excellent＂, ＂good＂, ＂average＂, and ＂poor＂-quality embryos. The relationship between these embryo grades and the achieved pregnancy outcomes was then analyzed via the Chi-square and logistic regression tests. Results： For embryo grades of excellent, good, average and poor, the clinical pregnancy rates were 65.0%. 50.3%, 50.3% and 33.3%. respectively; and the live-birth rates were 50.0%, 49.7%, 42.3% and 25.0%, respectively. Both the clinical pregnancy ratc （x2= 21.28. P = 0.001） and live-birth rate （x2 = 13.50, P 〈 0.001） increased with the overall blastocyst grade. Both rates were significanlly higher after the transfer era blastocyst that exhibited either an A-grade or B-grade TE, and similarly, an A-grade ICM. than after the transfer el a blastocyst that exhibited a C-grade TE and/or ICM. The degree of blastocysl expansion had no apparent effect on the clinical pregnancy or live-birth rate. All odds ratio were adjusted for patient age, body mass index, length （years） of infertility history, and infertility type. Conclusions： A higher overall euploid blas
