S1P受体激动剂FTY720干扰孕鼠体内DC分布从而诱导妊娠免疫耐受  

The sphingosine 1-phosphate receptor agonist FTY720 interferes the distribution of DC and induces the maternal fetal immune tolerance

作　　者：熊苗[1] 徐亮[2] 李莉[1] 刘阳[1] 周芳芳[1] 黄红玲[1] 朱洁萍[1] 

机构地区：[1]上海交通大学附属第六人民医院妇产科,200233 [2]上海交通大学医学院附属国际和平妇幼保健院,200030

出　　处：《免疫学杂志》2018年第1期41-47,共7页Immunological Journal

基　　金：国家自然科学基金(81200477);上海市第六人民医院医疗集团课题

摘　　要：目的探讨S1P受体激动剂FTY720在降低自然流产模型孕鼠胚胎丢失率进程中的作用及其可能的机制。方法以自然流产模型孕鼠为研究对象,观察腹腔注射FTY720对自然流产模型孕鼠胚胎丢失率的影响,RT-PCR检测DC表面S1PR的表达,流式细胞术及免疫组化检测孕鼠外周血及局部组织中DC数量、成熟度及其表面相应趋化因子CCL19及其受体CCR7的表达情况,趋化实验验证FTY720对DC细胞趋化能力的影响。结果 1)FTY720对正常妊娠模型孕鼠的胚胎丢失率无明显影响(P<0.05),过继转移FTY720能明显降低自然流产模型孕鼠的胚胎丢失率(P<0.05);2)DC表面存在S1P受体的广泛表达,S1P受体激动剂FTY720减少了DC表面趋化因子及其受体的表达(P<0.05),致使趋化至母胎界面DC的数量显著减少(P<0.05);3)FTY720对DC细胞的分化及凋亡率均无明显影响(P>0.05)。结论 FTY720可能通过下调DC表面趋化因子受体CCR7的表达而使趋化至母胎界面的DC数量减少,最终诱导母胎免疫耐受。To investigate the induction mechanism of FTY720, an agonist of the sphingosine 1-phos-phate （SIP） receptor, in the maternal fetal immune tolerance, the effect of adoptive transferring of FTY720 treated DCs on embryo loss rate was calculated. Immunohistochemistry and flow cytometric analysis were employed to analyze the apoptosis and migration of DCs and the expression of CCR7 on DCs, Chemotaxis assay was performed to verify the effect of FTY720 on chemotaxis of DCs. Data showed that FTY720 had no significant effect on the embryo loss rate in normal pregnant rats. In contrast, adoptive transferring of FTY720 could significantly reduce the embryo loss rate of the spontaneous abortion mouse model （P〈0.05）. DCs from blood and bone marrow were all expressed S1PRs, while FTY720 administration down-regulated CCR7 expression on DC, thus reduced transendothelial migration of DC to CCL19 （P〈0.05）. FTY720 did not interfere with DC differentiation or affect the apoptotic death of DC （P〉 0.05）. We concluded that FTY720 induces maternal fetal immune tolerance through down-regulation of CCR7 expression on DC, which reduces the migration of DCs to maternal-fetal interface tissue.

关 键 词：趋化因子受体7 趋化因子19 妊娠免疫耐受 FTY720 S1P受体 

分 类 号：R392.9[医药卫生—免疫学]