Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-alpha or IL-4

Eur J Immunol. 2009 Jan;39(1):56-66. doi: 10.1002/eji.200738098.

Abstract

Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-alpha ((IFN)DC) or IL-4 ((IL-4)DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that (IFN)DC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature (IL-4)DC co-express both constitutive (beta1, beta2, and beta5) and inducible subunits, as shown by Western blotting analysis. In addition, immature (IFN)DC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than (IL-4)DC. The different proteasome profiles of (IFN)DC and (IL-4)DC were associated with a greater ability of (IFN)DC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / immunology
  • ATP-Binding Cassette Transporters / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Epitopes / immunology
  • Humans
  • Immunologic Factors / pharmacology
  • Interferon-alpha / pharmacology
  • Interleukin-4 / pharmacology
  • Intracellular Calcium-Sensing Proteins / drug effects
  • Intracellular Calcium-Sensing Proteins / immunology
  • Intracellular Calcium-Sensing Proteins / metabolism
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / immunology
  • Membrane Transport Proteins / metabolism
  • Monocytes / enzymology*
  • Monocytes / immunology
  • Multienzyme Complexes / biosynthesis*
  • Multienzyme Complexes / drug effects
  • Proteasome Endopeptidase Complex / biosynthesis*
  • Proteasome Endopeptidase Complex / drug effects

Substances

  • ATP-Binding Cassette Transporters
  • Epitopes
  • Immunologic Factors
  • Interferon-alpha
  • Intracellular Calcium-Sensing Proteins
  • Membrane Transport Proteins
  • Multienzyme Complexes
  • tapasin
  • Interleukin-4
  • LMP7 protein
  • Proteasome Endopeptidase Complex