DC-SIGN expression in Hofbauer cells may play an important role in immune tolerance in fetal chorionic villi during the development of preeclampsia

J Reprod Immunol. 2017 Nov:124:30-37. doi: 10.1016/j.jri.2017.09.012. Epub 2017 Sep 28.

Abstract

Immune tolerance at feto-maternal interfaces is a complex phenomenon. Although maternal decidual macrophages are well-known immune cells, little is known about fetal-derived macrophages (Hofbauer cells) within chorionic villi. Preeclampsia (PE) is a major cause of maternal mortality in the field of obstetrics, and the innate immunological role of maternal decidual macrophages is well known. In this study, we assessed the differential phenotypes and marker expression in fetal macrophages, known as dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)-positive Hofbauer cells. We compared Hofbauer cell properties between normal and PE placenta chorionic villi and performed sequential staining of DC-SIGN, CD14, and CD68 to evaluate the existence of Hofbauer cells. Furthermore, to evaluate the immunological function of these cells, we stained the cells for CD163, a marker of immunoregulatory type 2 (M2) macrophages. Additionally, we examined the expression of the immunosuppressive cytokine interleukin (IL)-10, which is known to be produced by M2 macrophages. DC-SIGN+/CD14+, DC-SIGN+/CD68+, and CD163+/DC-SIGN+ cells were quantified based on photomicrographs. The results showed that CD14, CD163, DC-SIGN, and IL-10 levels were significantly downregulated in PE compared with normal. Additionally, CD163+/DC-SIGN+ Hofbauer cells were significantly less frequent in PE than in normal. DC-SIGN Hofbauer cells produced IL-10 at lower levels in the PE than in the normal. Thus, we speculate that fetal-derived Hofbauer cells may play an important role in normal pregnancy with immunosuppressive effects based on their M2 macrophage characteristics to maintain immune tolerance during pregnancy. Additionally, in PE, these functions were defective, supporting the roles of these macrophages in PE development.

Keywords: Dendritic cell-specific ICAM-grabbing non-integrin; Hofbauer cell; Immune tolerance; Preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Chorionic Villi / pathology*
  • Female
  • Gene Expression Regulation
  • Histiocytes / immunology
  • Histiocytes / metabolism*
  • Humans
  • Immune Tolerance
  • Interleukin-10 / metabolism
  • Lectins, C-Type / metabolism*
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / immunology
  • Pre-Eclampsia / immunology*
  • Pregnancy
  • Receptors, Cell Surface / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Interleukin-10