Stromal cells from human decidua exert a strong inhibitory effect on NK cell function and dendritic cell differentiation

PLoS One. 2014 Feb 20;9(2):e89006. doi: 10.1371/journal.pone.0089006. eCollection 2014.

Abstract

Stromal cells (SC) are an important component of decidual tissues where they are in strict proximity with both NK and CD14(+) myelomonocytic cells that play a role in the maintenance of pregnancy. In this study we analyzed whether decidual SC (DSC) could exert a regulatory role on NK and CD14(+) cells that migrate from peripheral blood (PB) to decidua during pregnancy. We show that DSCs inhibit the IL15-mediated up-regulation of major activating NK receptors in PB-derived NK cells. In addition, the IL15-induced NK cell proliferation, cytolytic activity and IFN-γ production were severely impaired. DSCs sharply inhibited dendritic cells differentiation and their ability to induce allogeneic T cell proliferation. Indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) mediated the inhibitory effect of DSCs. Our results strongly suggest an important role of DSCs in preventing potentially dangerous immune response, thus contributing to maintenance of pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Cell Differentiation / immunology*
  • DNA Primers / genetics
  • Decidua / cytology*
  • Decidua / immunology
  • Dendritic Cells / immunology*
  • Dinoprostone / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance / immunology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interleukin-15 / metabolism
  • Killer Cells, Natural / immunology*
  • Pregnancy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / immunology*

Substances

  • Antibodies, Monoclonal
  • DNA Primers
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-15
  • Dinoprostone

Grants and funding

This work was supported by grants awarded by Associazione Italiana Ricerca sul Cancro (AIRC): IG 2010 project n. 10225 (LM), and “Special Program Molecular Clinical Oncology 5×1000” project n. 9962 (LM), Ministero dell’Istruzione, Università e Ricerca (MIUR): MIUR-FIRB 2003 project RBLA039LSF-001 (LM), MIURPRIN2009 project 2009T4TC33_004 (MCM), Ministero della Salute: RF2006-Ricerca Oncologica-Project of Integrated Program 2006–08, agreements n. RO strategici 3/07 (LM) and RO strategici 8/07 (MCM), RF-IG-2008–1200689 (MCM), and Progetto Ricerca Ateneo 2013 (PV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.