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

Journal article

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.

Authors: Gasparini, C; Foxwell, B; Feldmann, M

• Publication status: Published
• Journal: European journal of immunology
• Volume: 39
• Issue: 8
• Pages: 2215-2223
• Publication date: 2009-08-01
• DOI: 10.1002/eji.200939209
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Adenoviridae; I-kappa B Proteins; Chemokine CCL19; Antigen-Presenting Cells; Base Sequence; Binding Sites; NF-kappa B p50 Subunit; Interleukin-10; Dendritic Cells; Blotting, Western; Cell Differentiation; Green Fluorescent Proteins; Chemokine CXCL13; Interleukin-6; Transcription Factor RelB; Tumor Necrosis Factor-alpha; Microscopy, Fluorescence; Lipopolysaccharides; Transfection; Enzyme-Linked Immunosorbent Assay; Humans; Protein Binding; Chemokine CCL22