Involvement of the Tim-3 Pathway in the Pathogenesis of Pre-Eclampsia
Involvement of the Tim-3 Pathway in the Pathogenesis of Pre-Eclampsia
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Tim-3 通路参与先兆子痫的发病机制
DOI：
10.1007/s43032-021-00675-3
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发表时间：
2021-07
影响因子：
2.9
通讯作者：
Zhang Ying
中科院分区：
文献类型：
--
作者：
Wang Songcun;Chen Chunqin;Sun Fengrun;Li Mengdie;Du Meirong;Li Xiaotian;Zhang Ying
目前早期诊断和预防先兆子痫（PE）的方法有限;唯一可用的明确治疗方法是开始分娩和完全切除胎盘。免疫系统的不适当激活被认为在PE中起相当大的作用。T细胞免疫球蛋白粘蛋白-3（Tim-3）在妊娠早期调节免疫应答并在母胎耐受中发挥重要作用。本研究旨在探讨Tim-3在正常妊娠晚期母胎串扰中的功能调节及其在PE发病机制中的可能作用。我们发现蜕膜免疫细胞上的Tim-3表达与抗炎细胞因子的产生相关。Tim-3通路阻断导致更高的IFN-γ，但更低的IL-4和IL-10产生。使用HTR 8/SVneo细胞和人脐静脉内皮细胞之间的管形成测定，我们发现Tim-3途径阻断抑制管形成，并通过添加重组IL-4和/或IL-10逆转。先兆子痫患者在蜕膜和外周免疫细胞（特别是外周CD 8 +T细胞）上均显示出减少的Tim-3表达。因此，我们认为Tim-3信号异常导致母胎界面的免疫失衡，并可能通过影响子宫螺旋动脉重塑参与PE的进展。本研究将Tim-3信号通路的调控功能扩展到孕晚期，为PE的早期预警和治疗策略提供了新的靶点。
Current methods of early diagnosis and prevention of pre-eclampsia (PE) are limited; the only available definite treatment is the initiation of delivery and complete removal of the placenta. Inappropriate activation of the immune system is thought to play considerable roles in PE. T cell immunoglobulin mucin-3 (Tim-3) has been reported to regulate immune responses and play important roles in maternal-fetal tolerance during early pregnancy. In this study, we investigated the functional regulation of Tim-3 in the maternal-fetal crosstalk during 3rd-trimester healthy pregnancy and its possible role in the pathogenesis of PE. We found that Tim-3 expression on decidual immune cells was associated with production of anti-inflammatory cytokines. Tim-3 pathway blockade resulted in higher IFN-γ but lower IL-4 and IL-10 production. Using a tube formation assay between HTR8/SVneo cells and human umbilical vein endothelial cells, we found that Tim-3 pathway blockade inhibits tube formation and reversed by addition of recombinant IL-4 and/or IL-10. Pre-eclamptic patients showed reduced Tim-3 expression on both decidual and peripheral immune cells (especially on peripheral CD8+T cells). Therefore, we proposed that abnormal Tim-3 signal resulted in immunological imbalance at the maternal-fetal interface and may be involved in the progress of PE by affecting uterine spiral artery remodeling. Our study expanded the regulatory function of Tim-3 signaling pathway to the 3rd-trimester pregnancy and provided a new target for early warning and therapeutic strategies of PE.
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影响因子：
3.7
作者：
Sakhdari A;Mujib S;Vali B;Yue FY;MacParland S;Clayton K;Jones RB;Liu J;Lee EY;Benko E;Kovacs C;Gommerman J;Kaul R;Ostrowski MA
通讯作者：
Ostrowski MA
DOI：
10.1159/000087912
发表时间：
2005-01-01
期刊：
IMMUNOLOGY OF PREGNANCY
影响因子：
--
作者：
Matthiesen, L;Berg, G;Sharma, S
通讯作者：
Sharma, S
影响因子：
7.3
作者：
S. Robertson;Ella S. Green;Alison S. Care;L. M. Moldenhauer;J. Prins;M. L. Hull;S. Barry;G. Dekker-G.-Dekke
通讯作者：
S. Robertson;Ella S. Green;Alison S. Care;L. M. Moldenhauer;J. Prins;M. L. Hull;S. Barry;G. Dekker-G.-Dekke
DOI：
10.1016/s0140-6736(05)17987-2
发表时间：
2005-03
期刊：
The Lancet
影响因子：
--
作者：
B. Sibai;G. Dekker;M. Kupferminc
通讯作者：
B. Sibai;G. Dekker;M. Kupferminc
DOI：
10.1007/978-3-030-16481-2_34
发表时间：
2019
期刊：
Textbook of Vascular Medicine
影响因子：
--
作者：
D. Carty
通讯作者：
D. Carty