Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immu...Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.展开更多
目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3...目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3分子的表达情况,ELISA法检测移植后患者细胞因子Galectin-9、IFN-γ、IL-4、TGF-β和IL-17的动态变化。结果根据西雅图国际诊断标准,移植术后有14例患者发生aGVHD,22例患者未发生aGVHD。①未发生aGVHD患者移植后30~90 d CD4^(+)T细胞百分比均低于健康对照组(P<0.05);未发生aGVHD患者移植后血清中细胞因子Galectin-9、TGF-β、IFN-γ、IL-4和IL-17水平呈现逐渐增高的趋势,Galectin-9和TGF-β水平在移植后60 d达到正常值(P>0.05),IFN-γ、IL-4和IL-17在移植后第90天恢复到正常水平(P>0.05)。Spearman相关分析结果显示Galectin-9与TGF-β变化水平呈正相关(r=0.651,P=0.001);②发生aGVHD患者外周血中Tim-3^(+)CD4^(+)T细胞的百分比和IFN-γ、IL-17水平明显高于不发生aGVHD患者(P<0.01);不发生aGVHD患者的Galectin-9和TGF-β水平更高(P<0.05)。Spearman相关分析结果显示Tim-3^(+)CD4^(+)T细胞的百分比与IFN-γ水平呈正相关(r=0.631,P=0.015)。结论单倍体相合外周血造血干细胞移植后细胞因子Galectin-9和TGF-β的早期快速重建可以避免或减缓aGVHD的发生,移植后动态监测Tim-3^(+)CD4^(+)T细胞持续较多而血清中Galectin-9水平下降可能预示着aGVHD的发生。展开更多
文摘Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.
文摘目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3分子的表达情况,ELISA法检测移植后患者细胞因子Galectin-9、IFN-γ、IL-4、TGF-β和IL-17的动态变化。结果根据西雅图国际诊断标准,移植术后有14例患者发生aGVHD,22例患者未发生aGVHD。①未发生aGVHD患者移植后30~90 d CD4^(+)T细胞百分比均低于健康对照组(P<0.05);未发生aGVHD患者移植后血清中细胞因子Galectin-9、TGF-β、IFN-γ、IL-4和IL-17水平呈现逐渐增高的趋势,Galectin-9和TGF-β水平在移植后60 d达到正常值(P>0.05),IFN-γ、IL-4和IL-17在移植后第90天恢复到正常水平(P>0.05)。Spearman相关分析结果显示Galectin-9与TGF-β变化水平呈正相关(r=0.651,P=0.001);②发生aGVHD患者外周血中Tim-3^(+)CD4^(+)T细胞的百分比和IFN-γ、IL-17水平明显高于不发生aGVHD患者(P<0.01);不发生aGVHD患者的Galectin-9和TGF-β水平更高(P<0.05)。Spearman相关分析结果显示Tim-3^(+)CD4^(+)T细胞的百分比与IFN-γ水平呈正相关(r=0.631,P=0.015)。结论单倍体相合外周血造血干细胞移植后细胞因子Galectin-9和TGF-β的早期快速重建可以避免或减缓aGVHD的发生,移植后动态监测Tim-3^(+)CD4^(+)T细胞持续较多而血清中Galectin-9水平下降可能预示着aGVHD的发生。
