International Collaborative Jointed Laboratory of Maternal and Fetal Medicine, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
State Key Laboratory of Maternal, Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China.
Reprod Sci. 2022 Jun;29(6):1764-1775. doi: 10.1007/s43032-021-00803-z. Epub 2021 Dec 2.
The objective of this study is to investigate the effect of IL-27 on Th1 cells infiltration in human fetal membranes (FMs) in preterm labor (PL). The expression of Th1 cells specific transcription factor (T-bet), Th1 cells infiltration related molecules (CXCL9, CXCL10, CXCL11, and ICAM-1), and IL-27 receptor α subunit (IL-27Rα) was compared in human FMs from pregnant women in PL group and term labor (TL) group. In vitro, rhIL-27 was added to the culture medium of amniotic epithelial cells (WISH cells) to detect the expression of CXCL9, CXCL10, CXCL11, and ICAM-1. Furthermore, the underlying signaling pathway was detected by single-sample gene set enrichment analysis and western blot analysis. The expression of T-bet and CXCL9, CXCL10, CXCL11, and ICAM-1 as well as IL-27Rα was higher in human FMs from PL group than TL group. In vitro, rhIL-27 could upregulate the expression of CXCL9, CXCL10, CXCL11, and ICAM-1 in WISH cells. Using gene-set enrichment analysis of FMs, JAK/STAT signaling pathway was found to be activated by IL-27 signaling in PL. Using western blot analysis, JAK2/STAT1/STAT3 signaling pathway was confirmed to be enhanced in rhIL-27 treated WISH cells. In addition, AG490 (JAK2 inhibitor) could inhibit the secretion of CXCL9, CXCL10, and CXCL11 in WISH cells stimulated by rhIL-27. Our results suggested that IL-27 may promote Th1 cells infiltration in human FMs in PL, by promoting the expression of CXCL9, CXCL10, and CXCL11 at least partly through JAK2/STAT1/STAT3 signaling pathway.
本研究旨在探讨白细胞介素-27（IL-27）对早产（PT）患者胎膜中 Th1 细胞浸润的影响。比较了 PT 组和足月产（TL）组孕妇胎膜中 Th1 细胞特异性转录因子（T-bet）、Th1 细胞浸润相关分子（CXCL9、CXCL10、CXCL11 和 ICAM-1）和 IL-27 受体α亚基（IL-27Rα）的表达。体外向羊膜上皮细胞（WISH 细胞）培养基中加入 rhIL-27，检测 CXCL9、CXCL10、CXCL11 和 ICAM-1 的表达。此外，通过单样本基因集富集分析和 Western blot 分析检测潜在信号通路。PT 组胎膜中 T-bet 和 CXCL9、CXCL10、CXCL11 和 ICAM-1 的表达以及 IL-27Rα的表达均高于 TL 组。体外 rhIL-27 可上调 WISH 细胞中 CXCL9、CXCL10、CXCL11 和 ICAM-1 的表达。通过对胎膜的基因集富集分析，发现 IL-27 信号通过 JAK/STAT 信号通路在 PL 中被激活。通过 Western blot 分析，证实 rhIL-27 处理的 WISH 细胞中 JAK2/STAT1/STAT3 信号通路增强。此外，AG490（JAK2 抑制剂）可抑制 rhIL-27 刺激的 WISH 细胞中 CXCL9、CXCL10 和 CXCL11 的分泌。我们的研究结果表明，IL-27 可能通过促进 CXCL9、CXCL10 和 CXCL11 的表达，至少部分通过 JAK2/STAT1/STAT3 信号通路，促进 PL 患者胎膜中 Th1 细胞的浸润。
