FTY720调控DC表面趋化因子及其受体表达的机制研究  

Study on the mechanism of FTY720regulating the expression of chemokines and their receptors on the surface of DC

作　　者：熊苗 包春玲 周芳芳 XIONG Miao;BAO Chun-ling;ZHOU Fang-fang(Department of Obstetrics and Gynecology,Sixth People’s Hospital Affiliated to Shanghai Medical College,Shanghai200123,China)

机构地区：[1]上海健康医学院附属第六人民医院东院妇产科,上海200123

出　　处：《中国实验诊断学》2020年第12期2029-2033,共5页Chinese Journal of Laboratory Diagnosis

基　　金：国家自然科学基金项目(81200477);上海健康医学院师资百人库资助项目(B1-0200-19-311006-07);上海健康医学院种子基金资助项目(SFP-18-22-14-003)。

摘　　要：目的探讨S1P受体激动剂FTY720对自然流产模型孕鼠胚胎丢失率的影响及其可能机制。方法建立自然流产模型孕鼠,观察FTY720对胚胎丢失率的影响;构建过表达1-磷酸鞘氨醇(S1P)及S1P-siRNA慢病毒载体并转染树突状细胞(DC),观察过继转移慢病毒前后自然流产模型孕鼠胚胎丢失率的变化及外周血、蜕膜组织DC数量、CCL19及CCR7表达情况、DC分化、凋亡及趋化情况。结果FTY720可显著降低胚胎丢失率,同时抑制DC表面趋化因子及其受体的表达(P<0.05);过继转移S1P-siRNA-DC对FTY720抑制DC表面趋化因子及受体无明显影响(P>0.05),过继转移过表达S1P-DC能有效提高FTY720对DC表面趋化因子受体的抑制作用(P<0.05)。结论FTY720可能通过阻断S1P信号通路干扰孕鼠体内DC表面趋化因子及其受体表达,减少DC数量,诱导妊娠免疫耐受。Objective To investigate the effect of FTY720 on the embryo loss rate of pregnant mice in spontaneous abortion model and its possible mechanism.Methods Established a spontaneous abortion model of pregnant mice and observe the effect of FTY720 on the rate of embryo loss;constructed S1 Pand S1 P-siRNA lentiviral vectors to transfect DC respectively,observed the number of DCs in peripheral blood and decidua tissue before and after adoptive transfer of lentivirus,the expression of CCL19 and CCR7,DC differentiation,apoptosis and chemotaxis.Results FTY720 can significantly reduce the rate of embryo loss(P<0.05).Adoptive transfer of S1 P-siRNA-DC has no significant effect on FTY720′s inhibition of DC surface chemokines and receptors(P>0.05).Adoptive transfer of S1 P-DC can effectively increase the inhibitory effect of FTY720 on DC surface chemokine receptors(P<0.05).Conclusion FTY720 may interfere with the expression of chemokines and their receptors on the surface of DCs in pregnant mice by blocking the S1 Psignaling pathway,reducing the number of DCs and inducing immune tolerance.

关 键 词：妊娠免疫耐受 FTY720 树突状细胞 趋化因子 

分 类 号：R392.9[医药卫生—免疫学]