Decidual stromal cells maintain decidual macrophage homeostasis by secreting IL-24 in early pregnancy

Am J Reprod Immunol. 2020 Aug;84(2):e13261. doi: 10.1111/aji.13261. Epub 2020 May 29.

Abstract

Problem: The state of self-renewal and self-maintain of decidual macrophages would be important for immune homeostasis at the maternal-fetal interface. The roles of interleukin (IL)-24 derived from decidual stromal cells (DSCs) on decidual macrophages have not been explored.

Method of study: IL-24 expression in DSCs was interfered by lentivirus, and the transcription levels of IL-24 in DSCs were verified by real time (RT)-PCR. The levels of IL-24 receptors were determined by flow cytometry assays. The effect of recombination human IL-24 (rhIL-24) on the differentiation and apoptosis of macrophages was analyzed by flow cytometry in vitro. The viability of macrophages was detected by Cell Counting Kit-8 assays.

Results: The growth of DSCs was not affected obviously only by IL-24 knockdown while the growth of knockdown DSCs was inhibited significantly after co-cultured with decidual macrophages. The levels of IL-24 receptors (IL-20R1 and IL-22R1) were moderately to highly expressed on decidual macrophages and human macrophage cell line U937. The differentiation of decidual macrophages treated by rhIL-24 or co-cultured with IL-24 knockdown DSCs was not affected. Both apoptosis and viability of U937 cells were promoted by rhIL-24. The ratio of Bcl-2/Bax was down-regulated and Ki-67 was up-regulated by IL-24 treatment. The expression of Bcl-2/Bax was up-regulated while Ki-67 was down-regulated in U937 cells after co-cultured by IL-24 knockdown DSCs.

Conclusion: IL-24 secreted by DSCs promotes the renewal and homeostasis of decidual macrophages possibly via down-regulating the ratio of Bcl-2/Bax and up-regulating of the expression of Ki-67 in early pregnancy.

Keywords: IL-24; decidual macrophages; decidual stromal cells; homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Cell Differentiation
  • Cell Self Renewal
  • Decidua / cytology*
  • Decidua / immunology
  • Female
  • Gene Knockdown Techniques
  • Homeostasis
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Macrophages / immunology*
  • Pregnancy / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stromal Cells / immunology*
  • U937 Cells
  • Young Adult
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BCL2 protein, human
  • Interleukins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • interleukin-24