Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window

Reprod Biomed Online. 2014 Oct;29(4):481-9. doi: 10.1016/j.rbmo.2014.06.008. Epub 2014 Jul 10.

Abstract

Unexplained recurrent spontaneous abortion (RSA) might be caused by the mother's immunological rejection of the fetus. In this cross-sectional study, the percentage of T helper 17 (Th17), T regulatory (Treg) cells and their cytokines as the main players of immunomodulation in peripheral blood lymphocytes during the luteal phase of 20 women with unexplained RSA were compared with 20 normal non-pregnant women. The percentage of Treg cells in the former was significantly lower compared with controls. The percentage of Th17 cells in the former was higher than controls. Expression of IL-23, IL-17, IL-6 cytokines in the former was significantly higher than controls, but the higher expression of IL-21 was not significant. The gene expression of TGF-β and FoxP3 in the former was lower than controls. Significant positive correlations were found between the percentage of Th17 cells with IL-23, IL-6 and IL-17 and between expression of IL-23 and IL-6 and IL-17. IL-6 gene expression showed a significant positive correlation with IL-17. Therefore, imbalance of Th17-Treg cells and the consequent changes in cytokine expression might be implicated in the pathogenesis of unexplained RSA and may provide new insight into the immunoregulatory events at the maternal-fetal interface.

Keywords: IL-17; IL-21; IL-23; IL-6; TGF-β; unexplained recurrent spontaneous miscarriage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / immunology*
  • Abortion, Habitual / metabolism
  • Abortion, Habitual / pathology
  • Adult
  • Cells, Cultured
  • Cross-Sectional Studies
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Embryo Implantation*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation*
  • Humans
  • Iran
  • Linear Models
  • Luteal Phase*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Th17 Cells / pathology

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Messenger