IL-33/ST2 axis affects the polarization and efferocytosis of decidual macrophages in early pregnancy

Am J Reprod Immunol. 2018 Jun;79(6):e12836. doi: 10.1111/aji.12836. Epub 2018 Mar 3.

Abstract

Problem: To explore whether IL-33/ST2 axis modulates the polarization and efferocytosis of decidual macrophages (dMφs).

Method of study: The phenotype characteristics of dMφs from both normal pregnant women and recurrent spontaneous abortion (RSA) patients were determined by real-time polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Then, the efferocytosis and expression of IL-33 and its receptor (ST2) in dMφs were analyzed by FCM. Finally, the effects of sST2, a decoy receptor for IL-33 that inhibits the IL-33/ST2 signaling pathway, on the polarization and efferocytosis of dMφs and human macrophage cell line U937 were investigated.

Results: Compared with normal pregnancy, dMφs from RSA patients presented a M1 phenotype with high secretion of IL-33, whereas the expression of ST2 decreased. However, dMφs from RSA patients possessed a more powerful efferocytosis ability to clear the apoptotic decidual stromal cells (DSCs) compared with dMφs from normal pregnancy patients. Treatment with recombinant human sST2 led to the up-regulation of M1 bias and efferocytosis ability of both normal dMφs and U937.

Conclusion: This study indicates that IL-33 secreted by dMφs promotes M2 bias at the feto-maternal interface, and as a result, RSA might attribute to the disturbance of IL-33/ST2 axis and the enhancement of efferocytosis of dMφs subsequently.

Keywords: IL-33/ST2; RSA; decidual macrophages; efferocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / metabolism*
  • Abortion, Habitual / pathology
  • Abortion, Spontaneous / metabolism*
  • Abortion, Spontaneous / pathology
  • Adult
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Female
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / metabolism*
  • Interleukin-33 / metabolism*
  • Macrophages / metabolism*
  • Macrophages / pathology*
  • Phagocytosis / physiology*
  • Pregnancy
  • Signal Transduction / physiology
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • U937 Cells
  • Up-Regulation / physiology

Substances

  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33