Activation of liver X receptor sensitizes human dendritic cells to inflammatory stimuli

J Immunol. 2010 May 15;184(10):5456-65. doi: 10.4049/jimmunol.0902399. Epub 2010 Apr 21.


Dendritic cells (DCs) respond to changes in their lipid environment by altering gene expression and immunophenotype. Some of these alterations are mediated via the nuclear receptor superfamily. However, little is known about the contribution of liver X receptor (LXR) to DC biology. In this study, we present a systematic analysis of LXR, activated by synthetic ligands or naturally occurring oxysterols in developing human monocyte-derived DCs. We found that LXRs are present and can be activated throughout DC differentiation in monocyte- and blood-derived DCs. Administration of LXR-specific natural or synthetic activators induced target gene expression accompanied by increased expression of DC maturation markers, such as CD80 and CD86. In mature DCs, LXR activation augmented the production of inflammatory cytokines IL-12, TNF-alpha, IL-6, and IL-8 and resulted in an increased capacity to activate CD4+ T cell proliferation upon ligation with TLR4 or TLR3 ligands. These effects appear to be underpinned by prolonged NF-kappaB signaling. Supporting such an inflammatory role, we found that LXR positive DCs are present in reactive lymph nodes in vivo. We propose that activation of LXR represents a novel lipid-signaling paradigm that alters the inflammatory response of human DCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology*
  • Lipid Metabolism / immunology
  • Liver X Receptors
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Monocytes / cytology
  • Monocytes / immunology
  • Monocytes / metabolism
  • NF-kappa B / physiology
  • Orphan Nuclear Receptors / metabolism*
  • Orphan Nuclear Receptors / physiology
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Signal Transduction / immunology
  • Up-Regulation / immunology


  • Cytokines
  • Inflammation Mediators
  • Liver X Receptors
  • NF-kappa B
  • Orphan Nuclear Receptors
  • Protein Isoforms

Associated data

  • GEO/GSE8658