Tim-3在早期自然流产中的作用及与Th17/Treg细胞的关系

The role of Tim-3 in early spontaneous abortion and its relationship with Th17/Treg cells

目的:探讨T细胞免疫球蛋白粘蛋白分子-3(Tim-3)在早期自然流产中的作用及其与Th17/Treg细胞的关系。方法:选取2016年12月至2017年3月广州医科大学附属深圳沙井医院收治的30例早期自然流产患者作为研究组,另选取30例同期正常早孕自愿行人工流产者作为对照组。采集两组血液及子宫蜕膜,比较外周血单核细胞中Tim-3在CD4^+T、CD4^+T Th17、CD4^+T Treg细胞上的表达水平及Th17/Treg Ratio,分析Tim-3与Th17/Treg细胞相关性,并比较两组外周血与子宫蜕膜Tim-3、白细胞介素-6(IL-6)、IL-17、转化生长因子-β(TGF-β)水平。结果:研究组外周血单核细胞中CD4^+T Treg Tim-3低于对照组,CD4^+T Tim-3、CD4^+T Th17 Tim-3、Th17/Treg Ratio高于对照组(P<0.05);研究组Tim-3表达与Th17/Treg细胞呈正相关(r=0.898,P<0.05);研究组外周血Tim-3、IL-6、IL-17、TGF-β高于对照组(P<0.05);研究组子宫蜕膜Tim-3、IL-6、IL-17阳性表达率高于对照组(P<0.05);两组子宫蜕膜TGF-β阳性表达率无明显差异(P<0.05)。结论:早期自然流产中Tim-3呈现异常表达状态,与Th17/Treg细胞失衡、相关细胞因子改变有关,与Th17/Treg Ratio呈正相关,Tim-3有望成为临床判断早期自然流产发生的特异性指标。

Objective:To investigate the role of T cell immunoglobulin mucin-3(Tim-3)in early spontaneous abortion and its relationship with Th17/Treg cells.Methods:Thirty patients with early spontaneous abortion admitted to Shenzhen Shajing Hospital affiliated to Guangzhou Medical University between December2016 and March 2017 were enrolled as the study group,and a contemporary cohort of 30 women early in normal pregnancy who chose to undergo spontaneous abortion were recruited as the control group.Blood and decidua samples were collected from the two groups.The peripheral blood mononuclear cells(PBMC)expression levels of Tim-3 on CD4^+T,CD4^+T Th17,CD4^+T Treg cells and Th17/Treg ratio were compared between groups.The correlation between Tim-3 and Th17/Treg cell was analyzed.The levels of Tim-3,interleukin-6(IL-6),IL-17,and transforming growth factor-β(TGF-β)in peripheral blood and decidua of the two groups were also compared.Results:Compared with the control group,the study group showed lower PBMC expression level of CD4^+T Treg Tim-3,and higher expression levels of CD4^+T Tim-3,CD4^+T Th17 Tim-3 and higher Th17/Treg ratio(P<0.05).The expression of Tim-3 in the study group was positively correlated with Th17/Treg cells(r=0.898,P<0.05).The peripheral blood levels of Tim-3,IL-6,IL-17 and TGF-βin the study group were higher than those in the control group(P<0.05).The positive expression rates of Tim-3,IL-6 and IL-17 in the decidua of the study group were higher than those in the control group(P<0.05).There was no significant difference in the positive expression rate of TGF-βbetween the two groups(P>0.05).Conclusion:Tim-3 is abnormally expressed in early spontaneous abortion,which is related to Th17/Treg imbalance and alterations in certain cytokine,and positively correlated with Th17/Treg ratio.Tim-3 is promising as a specific marker for clinical determination of early spontaneous abortion.