RelB/p50 regulates CCL19 production, but fails to promote human DC maturation

Eur J Immunol. 2009 Aug;39(8):2215-23. doi: 10.1002/eji.200939209.

Abstract

DC, when fully matured are the APC best able to activate naïve T cells. Recently, we demonstrated using adenoviruses overexpressing IkappaBalpha and proteosome inhibitors that NF-kappaB is involved in DC activation, but the role of the individual subunits is still not clear. We investigated the role of the NF-kappaB subunits RelB and p50 in human DC activation using adenoviral vectors expressing RelB or p50. Nuclear RelB, in the form of RelB/p50, was active only in DC infected with both viruses, this induced the production of the soluble homeostatic chemokine CCL19, but not other homeostatic chemokines, particularly in LPS-matured DC. However, RelB/p50 did not affect the expression of costimulatory and antigen-presenting molecules, and increased the allogeneic mixed lymphocyte reaction only in LPS-matured DC. This enhanced mixed lymphocyte reaction is most likely due to enhanced CCL19 production, which sustains the interaction between mature DC and naïve T cells. In conclusion, we demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / metabolism*
  • Chemokine CCL22 / metabolism
  • Chemokine CXCL13 / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Microscopy, Fluorescence
  • NF-KappaB Inhibitor alpha
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism*
  • Protein Binding
  • Transcription Factor RelB / genetics
  • Transcription Factor RelB / metabolism*
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • CCL22 protein, human
  • CXCL13 protein, human
  • Chemokine CCL19
  • Chemokine CCL22
  • Chemokine CXCL13
  • I-kappa B Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • NFKBIA protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • NF-KappaB Inhibitor alpha
  • Green Fluorescent Proteins
  • Transcription Factor RelB