Inflammation-restraining effects of prostaglandin E2 on natural killer-dendritic cell (NK-DC) interaction are imprinted during DC maturation

Blood. 2011 Sep 1;118(9):2473-82. doi: 10.1182/blood-2010-09-307835. Epub 2011 Jun 29.

Abstract

Among prostaglandins (PGs), PGE2 is abundantly expressed in various malignancies and is probably one of many factors promoting tumor growth by inhibiting tumor immune surveillance. In the current study, we report on a novel mechanism by which PGE2 inhibits in vitro natural killer-dendritic cell (NK-DC) crosstalk and thereby innate and adaptive immune responses via its effect on NK-DC crosstalk. The presence of PGE2 during IFN-γ/membrane fraction of Klebsiella pneumoniae DC maturation inhibits the production of chemokines (CCL5, CCL19, and CXCL10) and cytokines (IL-12 and IL-18), which is cAMP-dependent and imprinted during DC maturation. As a consequence, these DCs fail to attract NK cells and show a decreased capacity to trigger NK cell IFN-γ production, which in turn leads to reduced T-helper 1 polarization. In addition, the presence of PGE2 during DC maturation impairs DC-mediated augmentation of NK-cell cytotoxicity. Opposed to their inhibitory effects on peripheral blood-derived NK cells, PGE2 matured DCs induce IL-22 secretion of inflammation constraining NKp44(+) NK cells present in mucosa-associated lymphoid tissue. The inhibition of NK-DC interaction is a novel regulatory property of PGE2 that is of possible relevance in dampening immune responses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / analogs & derivatives
  • Alprostadil / pharmacology
  • Bucladesine / pharmacology
  • Cell Differentiation
  • Cell Movement / drug effects
  • Cells, Cultured / drug effects
  • Cells, Cultured / immunology
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytotoxicity, Immunologic / drug effects
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dinoprostone / pharmacology*
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunosuppression Therapy
  • Inflammation / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Klebsiella pneumoniae / immunology
  • Misoprostol / pharmacology
  • Palatine Tonsil / cytology
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Chemokines
  • Cytokines
  • Misoprostol
  • Bucladesine
  • Interferon-gamma
  • Alprostadil
  • butaprost
  • Dinoprostone