Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system

Int J Biochem Cell Biol. 2009 May;41(5):1205-15. doi: 10.1016/j.biocel.2008.10.023. Epub 2008 Nov 5.


Dendritic cell maturation is the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T cell responses. Although some mechanistic aspects of DC maturation have begun to be characterised, very little is known about the genetic events regulating the ubiquitin-proteasome system which plays a key role at various levels of the immune response. Therefore, we here investigated the expression of more than 1000 genes related to the ubiquitin-proteasome system in maturing dendritic cells following various stimuli and identified a specific set of transcripts induced by lipopolysaccharide and/or Poly(I:C) which is largely distinct from that induced by CD40 ligand or pro-inflammatory cytokines. This group of genes was dependent on a type I interferon autocrine loop and included E1 and E2 enzymes, E3-ligases, de-ubiquitylating enzymes, proteasome components as well as the ubiquitin-like modifiers ISG15 and FAT10. We further demonstrate that the increased expression of the E2 enzyme UBE2L6 (UbcH8) is required for efficient antigen cross-presentation by dendritic cells. In summary, our data underline the importance of remodelling the ubiquitin-proteasome system for dendritic cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • CD40 Ligand / pharmacology
  • Cross-Priming / immunology
  • Cytokines / immunology
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Silencing
  • Humans
  • Lipopolysaccharides / pharmacology
  • Poly I-C / pharmacology
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Endopeptidase Complex / metabolism
  • Ubiquitin / genetics
  • Ubiquitin / immunology*
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes / biosynthesis
  • Ubiquitin-Conjugating Enzymes / deficiency
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitins / immunology
  • Ubiquitins / metabolism


  • Cytokines
  • Lipopolysaccharides
  • UBD protein, human
  • Ubiquitin
  • Ubiquitins
  • CD40 Ligand
  • UBE2L6 protein, human
  • Ubiquitin-Conjugating Enzymes
  • Proteasome Endopeptidase Complex
  • Poly I-C