Pathophysiology of unexplained recurrent pregnancy loss, preterm labor and preeclampsia from the viewpoint of reproductive immunology

从生殖免疫学角度探讨不明原因反复流产、早产和先兆子痫的病理生理学

• 批准号: 20390431
• 负责人: SAITO Shigeru
• 金额: $ 12.31万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390431/
• 关键词: 制御性T細胞; 妊娠; 着床不全; 流産; 早産; 妊娠高血圧腎症; IL-17; 制御性NK細胞; 妊娠高血圧症候群; Granulysin

T-helper (Th) cells play a central role in modulating immune responses. We discuss the pathophysiology of unexplained recurrent pregnancy loss, preterm labor and preeclampsia from the viewpoint of new Th1/Th2/Th17 and regulatory T (Treg) cell paradigm. We have reported that Treg cells play an essential role for maintenance of allogeneic pregnancy in early pregnancy, but not in late pregnancy. We also found that paternal antigen-specific Treg cells increase in uterine draining lymphonodes before the implantation and in uterus after implantation. We have found NKreg cells increase in the pregnant uterus and they express CD25 on their surface. They produce immunosuppressive cytokines such as IL-10 and TGFβ. Th17 cells increased in the uterus of preterm labor cases with severe chorioamnionitis and of spontaneous abortion cases in late stage, and there were significant positive correlation between Th17 cells number and neutrophil number. IL-17 also augment the TNF-α-induced IL-8 secretion by amniotic mesenchymal cells in a dose dependent manner. In preeclampsia, we found the production of VEGF and Galectin-1 by peripheral blood-T cells and -NK cells was decreased suggesting that angiogenesis and tolerance induction systems are dysregulated in preeclampsia.

辅助性 T (Th) 细胞在调节免疫反应中发挥着核心作用。我们从新的 Th1/Th2/Th17 和调节性 T (Treg) 细胞范式的角度讨论不明原因的复发性流产、早产和先兆子痫的病理生理学。我们报道Treg细胞在妊娠早期对维持同种异体妊娠发挥重要作用，但在妊娠晚期则不然。我们还发现，在着床前和着床后子宫内，父本抗原特异性 Treg 细胞在子宫引流淋巴结中增加。我们发现怀孕子宫中的 NKreg 细胞增多，并且它们的表面表达 CD25。它们产生免疫抑制细胞因子，例如 IL-10 和 TGFβ。严重绒毛膜羊膜炎早产病例和晚期自然流产病例子宫内Th17细胞增多，且Th17细胞数量与中性粒细胞数量呈显着正相关。 IL-17 还以剂量依赖性方式增强羊膜间充质细胞 TNF-α 诱导的 IL-8 分泌。在先兆子痫中，我们发现外周血 T 细胞和 NK 细胞产生的 VEGF 和 Galectin-1 减少，表明先兆子痫中血管生成和耐受诱导系统失调。

项目成果

Gestational choriocarcinoma in one placenta of dichorionic diamniotic twins who showed severe anemia.

患有严重贫血的双绒毛膜双羊膜双胞胎的一个胎盘发生妊娠绒毛膜癌。

• 发表时间: 2009
• 期刊: Placenta 30
• 作者: Shiozaki A;Yoneda N;Yoneda S;Soeda Y;Hamashima T;Ishizawa S;Tamura K;Horikawa S;Higashiyama H;Yoshida T;Miyawaki T;Saito S.
• 通讯作者: Saito S.

Alpha I antitrypsin activity is decreased in human amniotic membrane in preterm premature rupture.

早产儿羊膜早破时，α I 抗胰蛋白酶活性降低。

• 发表时间: 2009
• 期刊: Mol Hum Reprod 15
• 作者: Yoneda-Izumi N.;Toda A.;Okabe M.;Takashima S.;Yoshida T.;Koichi I.;Saito S.;Nikaido T.
• 通讯作者: Nikaido T.

Granulysin produced by uterine natural killer cell induces apoptosis of extravillous trophoblast in spontaneous abortion.

自然流产中子宫自然杀伤细胞产生的颗粒溶素诱导绒毛外滋养层细胞凋亡。

• 发表时间: 2008
• 期刊: Am J Pathol. 173
• 作者: Nakashima A.;Shiozaki A.;Myojo S.;Ito M.;Tatematsu M.;Sakai M.;Takamori Y.;Ogawa K.;Nagata K.;Saito S.
• 通讯作者: Saito S.

Regulatory T and NK cells during pregnancy.

怀孕期间的调节性 T 细胞和 NK 细胞。

• 发表时间: 2010
• 作者: Sakamoto T;Ishibashi T;Ogura Y;Shiraga F;Takeuchi S;Yamashita H; Japanese Retina and Vitreous Society Triamcinolone Survey Group;Saito S.
• 通讯作者: Saito S.

腫瘍免疫と妊娠免疫の類似性

肿瘤免疫和妊娠免疫之间的相似之处

• 发表时间: 2010
• 作者: Tamaki Y;Iriyama A;Yanagi Y;木下茂(編集);齋藤滋
• 通讯作者: 齋藤滋