Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during ...Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.展开更多
Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of...Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of immunity, which attempts to reject and fight foreign bodies. This piqued the interest of biologists and immunologists, who set out to discover the immune system’s composition and mode of response in the uterus. According to several studies, natural killer (NK) cells are present in a significant percentage that differs from what is seen in peripheral blood. As a result, several scientific studies have been conducted on uterine NK cells, investigating their types, characteristics, receptors, secretions, and interactions with the surrounding environment. Research has also indicated the capacity of uterine NK cells to strike a balance between eradicating uterine infections and effectively contributing to different phases of pregnancy. Various studies have shown that NK cell activity is intimately related to the success or failure of pregnancy. In this review, we describe the uterine NK cell subtypes;decidual (dNK) cells and endometrial NK cells (eNK) cells and their important role during different phases of pregnancy.展开更多
目的探讨重度子痫前期Tim-3+CD56^+CD16^-NK细胞的表达及其对滋养细胞侵袭及血管内皮细胞成管能力的影响。方法分离重度子痫前期患者(sPE组)及正常妊娠孕产妇(Normal组)的胎盘蜕膜组织中单个核细胞,细胞流式检测蜕膜NK细胞(decidual NK ...目的探讨重度子痫前期Tim-3+CD56^+CD16^-NK细胞的表达及其对滋养细胞侵袭及血管内皮细胞成管能力的影响。方法分离重度子痫前期患者(sPE组)及正常妊娠孕产妇(Normal组)的胎盘蜕膜组织中单个核细胞,细胞流式检测蜕膜NK细胞(decidual NK cell,dNK)细胞所占比例;免疫磁珠分选CD56^+CD16^-NK细胞,细胞流式及RT-PCR实验检测Tim-3在其中的表达;将分选出的CD56^+CD16^-NK细胞分为3组:正常对照(Control)组,即来源于正常妊娠胎盘蜕膜组织中的dNK细胞;重度子痫前期(sPE)组,即来源于重度子痫前期胎盘蜕膜组织中的dNK细胞;Tim-3封闭(Tim-3-Fc)组,即加入Tim-3-Fc融合蛋白进行处理的正常妊娠胎盘蜕膜组织中的dNK细胞。采用ELISA、Transwell侵袭及小管形成实验分别检测上述3组细胞上清液中TNF-α、IL-6、IL-8、VEGF及IFN-γ的表达及其对HTR8侵袭能力及血管内皮细胞成管能力的影响。结果与Control组相比,sPE组中CD56^+CD16^-NK细胞占蜕膜组织单个核细胞比例显著减少(P<0.05);免疫磁珠可分选出纯度达90%以上CD56^+CD16^-NK细胞,且sPE组中Tim-3的表达丰度及Tim-3 mRNA表达水平均较Control组显著降低(P<0.05);ELISA结果显示与Control组相比,sPE组与Tim-3-Fc组dNK细胞上清液中TNF-α、IFN-γ表达均显著增加(P<0.05),而IL-6、IL-8、VEGF表达均明显降低(P<0.05);Transwell侵袭实验及成管实验结果表明,sPE组与Tim-3-Fc组HTR8细胞侵袭能力及HUVEC成管能力较Control组显著降低(P<0.05),但Tim-3-Fc组HTR8细胞侵袭能力及HUVEC成管能力较sPE组明显增强(P<0.05)。结论重度子痫前期患者Tim-3+CD56^+CD16^-NK的表达显著降低,其可能通过损害蜕膜NK细胞的分泌功能来抑制滋养细胞的侵袭及血管内皮细胞的成管能力,从而促进子痫前期的发展。展开更多
文摘Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.
文摘Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of immunity, which attempts to reject and fight foreign bodies. This piqued the interest of biologists and immunologists, who set out to discover the immune system’s composition and mode of response in the uterus. According to several studies, natural killer (NK) cells are present in a significant percentage that differs from what is seen in peripheral blood. As a result, several scientific studies have been conducted on uterine NK cells, investigating their types, characteristics, receptors, secretions, and interactions with the surrounding environment. Research has also indicated the capacity of uterine NK cells to strike a balance between eradicating uterine infections and effectively contributing to different phases of pregnancy. Various studies have shown that NK cell activity is intimately related to the success or failure of pregnancy. In this review, we describe the uterine NK cell subtypes;decidual (dNK) cells and endometrial NK cells (eNK) cells and their important role during different phases of pregnancy.
文摘目的探讨重度子痫前期Tim-3+CD56^+CD16^-NK细胞的表达及其对滋养细胞侵袭及血管内皮细胞成管能力的影响。方法分离重度子痫前期患者(sPE组)及正常妊娠孕产妇(Normal组)的胎盘蜕膜组织中单个核细胞,细胞流式检测蜕膜NK细胞(decidual NK cell,dNK)细胞所占比例;免疫磁珠分选CD56^+CD16^-NK细胞,细胞流式及RT-PCR实验检测Tim-3在其中的表达;将分选出的CD56^+CD16^-NK细胞分为3组:正常对照(Control)组,即来源于正常妊娠胎盘蜕膜组织中的dNK细胞;重度子痫前期(sPE)组,即来源于重度子痫前期胎盘蜕膜组织中的dNK细胞;Tim-3封闭(Tim-3-Fc)组,即加入Tim-3-Fc融合蛋白进行处理的正常妊娠胎盘蜕膜组织中的dNK细胞。采用ELISA、Transwell侵袭及小管形成实验分别检测上述3组细胞上清液中TNF-α、IL-6、IL-8、VEGF及IFN-γ的表达及其对HTR8侵袭能力及血管内皮细胞成管能力的影响。结果与Control组相比,sPE组中CD56^+CD16^-NK细胞占蜕膜组织单个核细胞比例显著减少(P<0.05);免疫磁珠可分选出纯度达90%以上CD56^+CD16^-NK细胞,且sPE组中Tim-3的表达丰度及Tim-3 mRNA表达水平均较Control组显著降低(P<0.05);ELISA结果显示与Control组相比,sPE组与Tim-3-Fc组dNK细胞上清液中TNF-α、IFN-γ表达均显著增加(P<0.05),而IL-6、IL-8、VEGF表达均明显降低(P<0.05);Transwell侵袭实验及成管实验结果表明,sPE组与Tim-3-Fc组HTR8细胞侵袭能力及HUVEC成管能力较Control组显著降低(P<0.05),但Tim-3-Fc组HTR8细胞侵袭能力及HUVEC成管能力较sPE组明显增强(P<0.05)。结论重度子痫前期患者Tim-3+CD56^+CD16^-NK的表达显著降低,其可能通过损害蜕膜NK细胞的分泌功能来抑制滋养细胞的侵袭及血管内皮细胞的成管能力,从而促进子痫前期的发展。
