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E-GEOD-9241 - Transcription profiling of human dendritic cells matured by cadherin reveals disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation

Status
Released on 16 June 2008, last updated on 2 May 2014
Organism
Homo sapiens
Samples (17)
Array (1)
Protocols (25)
Description
The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state “tolerogenic DCs”. Experiment Overall Design: We performed a genome-wide microarray analysis to study the expression profiles of DCs matured by CD as opposed to a conventional TLR agonist (E. coli, which stimulates multiple TLRs). RNA was isolated from human CD34+ DCs at various times after stimulation and used to probe Affymetrix U95Av2 chips. A time course was followed after various stimuli, with single chips used per time point. >700 genes were found differentially regulated upon maturation by either CD or bacterial stimulation. Cluster analysis revealed that after an early phase (1-3 hr) of similarity, expression profiles exhibited by the two sets of DCs diverged dramatically at later time points (>6 hr). A number of transcripts were markedly upregulated in the bacteria-stimulated set that remained relatively unchanged or actually decreased in the cluster-disrupted set. There were some transcripts upregulated in cluster-disrupted cells, however, with at least some of these increases prevented by adding anti-E-cadherin mAb under conditions that blocked maturation. Clearly, the transcriptional events induced by alteration of E-cadherin-mediated adhesion were quite distinct from those induced by TLR activation.
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Aimin Jiang, Ona Bloom, Satoru Ono, Weiguo Cui, Juli Unternaehrer, Shan Jiang, J Andrew Whitney, John Connolly, Jacques Banchereau, Ira Mellman. Immunity 27(4):610-24 (2007)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-9241.idf.txt
Sample and data relationshipE-GEOD-9241.sdrf.txt
Raw data (1)E-GEOD-9241.raw.1.zip
Processed data (1)E-GEOD-9241.processed.1.zip
Array designA-AFFY-1.adf.txt
R ExpressionSetE-GEOD-9241.eSet.r
Links