IL-27 Mediates Th1 Cells Infiltration in Fetal Membranes in Preterm Labor

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.