Article

Dendritic cells require the NF-kappaB2 pathway for cross-presentation of soluble antigens.

Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
The Journal of Immunology (impact factor: 5.79). 08/2008; 181(1):354-63. pp.354-63
Source: PubMed

ABSTRACT NF-kappaB-inducing kinase (NIK) is responsible for activation of the non-canonical p100 processing pathway of NF-kappaB activation. This kinase has been shown to be critical for activation of this pathway after signaling through several TNF family members including CD40. The functional importance of this pathway in CD40 and TLR-induced dendritic cell (DC) differentiation was studied in vivo in the alymphoplasia (Aly) mouse. The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-canonical pathway. We show that while MHC class II presentation and in vivo migration of Aly DCs is intact, these cells are unable to cross-prime CD8+ T cells to exogenous Ag. Gene expression array analysis of DCs matured in vivo indicates multiple defects in Ag processing pathways after maturation and provide a global view of the genes that are regulated by the NF-kappaB2 pathway in DCs. These experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag. In addition, our findings explain the profound immune unresponsiveness of the Aly mouse.

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    Article: A computational evaluation of over-representation of regulatory motifs in the promoter regions of differentially expressed genes.
    Guofeng Meng, Axel Mosig, Martin Vingron
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    ABSTRACT: Observed co-expression of a group of genes is frequently attributed to co-regulation by shared transcription factors. This assumption has led to the hypothesis that promoters of co-expressed genes should share common regulatory motifs, which forms the basis for numerous computational tools that search for these motifs. While frequently explored for yeast, the validity of the underlying hypothesis has not been assessed systematically in mammals. This demonstrates the need for a systematic and quantitative evaluation to what degree co-expressed genes share over-represented motifs for mammals. We identified 33 experiments for human and mouse in the ArrayExpress Database where transcription factors were manipulated and which exhibited a significant number of differentially expressed genes. We checked for over-representation of transcription factor binding sites in up- or down-regulated genes using the over-representation analysis tool oPOSSUM. In 25 out of 33 experiments, this procedure identified the binding matrices of the affected transcription factors. We also carried out de novo prediction of regulatory motifs shared by differentially expressed genes. Again, the detected motifs shared significant similarity with the matrices of the affected transcription factors. Our results support the claim that functional regulatory motifs are over-represented in sets of differentially expressed genes and that they can be detected with computational methods.
    BMC Bioinformatics 01/2010; 11:267. · 2.75 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Ag processing pathways
 
Aly DCs
 
Aly mouse
 
critical
 
cross-prime CD8+ T cells
 
exogenous Ag
 
functional importance
 
Gene expression array analysis
 
mediating cross-priming
 
MHC class II presentation
 
mutant NIK molecule
 
NF-kappaB-inducing kinase
 
NF-kappaB2 pathway
 
non-canonical p100 processing pathway
 
non-canonical pathway
 
pathway
 
profound immune unresponsiveness
 
soluble Ag
 
TLR-induced dendritic cell
 
TNF family members