Monophosphoryl lipid A induces bone marrow precursor cells to differentiate into myeloid-derived suppressor cells

Mol Med Rep. 2013 Oct;8(4):1074-8. doi: 10.3892/mmr.2013.1653. Epub 2013 Aug 27.

Abstract

Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) are important in the immune response. In vitro, DCs are derived from myeloid precursors by stimulation with granulocyte macrophage colony‑stimulating factor and interleukin‑4. Previous studies demonstrated that lipopolysaccharide (LPS) in combination with interferon‑γ inhibited DC development but enhanced MDSC functions. Monophosphoryl lipid A (MPL), derived from LPS, is a unique immunomodulatory Toll‑like receptor 4 agonist. In the present study, MPL was used to disturb DC differentiation from myeloid precursors and it was observed that prolonged stimulation with MPL led to the accumulation of MDSCs in vitro and in vivo. In conclusion, it was demonstrated that stimulation by MPL from the beginning of cell differentiation disturbed the development of DCs and led to the accumulation of MDSCs.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / physiology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / drug effects
  • Myeloid Cells / physiology*
  • Phagocytosis
  • Phenotype
  • T-Lymphocytes / physiology
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / metabolism

Substances

  • Cytokines
  • Lipid A
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • monophosphoryl lipid A