母胎界面树突状细胞CCL17和CCL22表达在母胎免疫耐受中的作用

目的: 检测非孕期子宫内膜和正常妊娠早期及复发性自然流产患者蜕膜中树突状细胞(DC)CCL17和CCL22的表达差异,探讨母胎界面DC在CD4⁺CD25⁺调节性T细胞(Treg)的募集及母胎免疫耐受微环境形成中的作用。方法: 正常早孕组人工流产时、复发性流产组清宫时取其蜕膜,正常未孕组行子宫切除时取其内膜组织。分离蜕膜或子宫内膜单个核细胞,体外诱导培养DC,用real-time PCR法分析3组DC CCL17和CCL22 mRNA的表达水平,ELISA法检测3组DC培养上清液中CCL17和CCL22蛋白的表达。结果: 正常早孕组蜕膜DC CCL17和CCL22 mRNA的表达分别为3.04±0.40和1.83±0.24,均高于正常未孕组(0.85±0.24和0.31±0.08,P<0.01)和复发性流产组(1.65±0.14和0.96±0.09,P<0.01)。正常早孕组蜕膜DC能够持续旺盛分泌趋化因子CCL17和CCL22,在培养的12~96 h内CCL17和CCL22的分泌量逐渐增多。同一时点早孕组DC分泌的CCL17和CCL22均明显高于未孕组和复发性流产组DC分泌的CCL17和CCL22(P<0.01)。结论: 正常妊娠后蜕膜DC表达CCL17和CCL22增强,DC可能通过高表达CCL17和CCL22而增强对CD4⁺CD25⁺Treg的趋化作用,从而在母胎界面的免疫耐受中发挥重要作用,蜕膜DC表达CCL17和CCL22下降可能与复发性自然流产的发病有关。

Role of CCL17 and CCL22 expression in dendritic cells in maternal-fetal immune tolerance

AIM: To determine the expression of CCL17 and CCL22 in dendritic cells(DC) from human decidua and endometria.METHODS: The decidua were collected from normal pregnant women undergoing induced abortion and recurrent spontaneous abortion(RSA) women undergoing early abortion.The endometria were cllected from non-pregnant women undergoing abdominal hysterectomy.The mononuclear cells in the decidua and endometria were isolated.DC were induced by GM-CSF and IL-4,cultured in vitro and identified.The expression of CCL17 and CCL22 in DC at mRNA and protein levels was analyzed by real-time PCR and ELISA.RESULTS: The mRNA levels of CCL17 and CCL22 in decidual DC in normal pregnancy group were 3.04±0.40 and 1.83±0.24,respectively,significantly higher than those in endometrial DC in non-pregnancy group(0.85±0.24 and 0.31±0.08,respectively,P<0.01) and those in decidual DC in RSA group(1.65±0.14 and 0.96±0.09,respectively,P<0.01).Decidual DC continually and strongly secreted CCL17 and CCL22.The levels of CCL17 and CCL22 in normal pregnancy group were significantly higher than those in non-pregnancy group and RSA group at the same culture time point(P<0.01).CONCLUSION: The expression of CCL17 and CCL22 in decidual DC in pregnant woman increases.This may attract more CD4+CD25+ regulatory T cells to decidua and play an important role in the establishment of maternal-fetal immune tolerance.