RelB/p50 regulates CCL19 production, but fails to promote human DC maturation.
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.
Gasparini
Chiara
C
Kennedy Institute of Rheumatology Division, School of Medicine, Imperial College London, London, UK.
Foxwell
Brian M J
BM
Feldmann
Marc
M
D000256:Adenoviridae / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism*; D054422:Chemokine CCL22 / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515482:CCL22 protein, human; C110663:CXCL13 protein, human; D054415:Chemokine CCL19; D054422:Chemokine CCL22; D054382:Chemokine CXCL13; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D049452:Green Fluorescent Proteins; D051841:Transcription Factor RelB