The expression of intracellular cytokines of decidual natural killer cells in unexplained recurrent pregnancy loss

Abstract

Objective

This study aims to investigate the expression levels of TNF-α, IFN-γ, IL-4, and IL-10 in dNK cells and determine whether or not the MAPK signal pathway is involved in the regulation of cytokine secretion by dNK cells at the maternal–fetal interface.

Methods

In this study, we collected decidua specimens from patients with apparently normal pregnant and unexplained recurrent pregnancy loss (URPL) and extracted dNK cells by enzymatic digestion. Then the expression of cytokines were analyzed by flow cytometry and Real-Time PCR respectively.

Results

The secretions of both IFN-γ and TNF-α in dNK cells in URPL were significantly higher than those in normal pregnancy. Furthermore, p38/MAPK inhibitors can inhibit the secretion of four cytokines in normal pregnancy, while in URPL cases, p38/MAPK inhibitors only significantly inhibit the secretion of IL-4 and IFN-γ. ERK inhibitors had no effect on the expression of all four cytokines and JNK/MAPK inhibitors varied on different cytokines.

Conclusion

URPL is associated with a NK1 cytokine profile. MAPK signaling pathway is involved in the regulation of cytokine secretion by decidual NK cells at maternal–fetal interface.

Keywords:

• Unexplained recurrent pregnancy loss
• maternal–fetal interface
• decidual natural killer cells
• mitogen-activated protein kinase signal pathway

Acknowledgements

We thank Ms Yanling Wang and her team at State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences for her expert technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81270733], and the Beijing Natural Science Foundation [grant number 7132097].