Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation

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PubMed ID: 17936032
Contact: James Andrew Whitney

Image:email_GSE9241.png
CGI Pharmaceuticals Inc.

Species: Homo sapiens
Platform: Affymetrix GeneChip Human Genome U95 Version [1 or 2] Set HG-U95A
Number of Samples: 17
Date Range: 07/03/2002 - 07/03/2002
Experiment Quality: 91.98
2.15 %
94.91
Link to Repository: GSE9241
Original Intensity Data: Download
Clean Intensity Data: Download
Original PLIER Data: Download
Clean PLIER Data: Download
Clean CEL Files: Download
Data Rank:

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”.

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.

Type: time-course, dendritic cell maturation


Contents

[edit] Contributors

  • Andrew Whitney
  • Aimin Jiang
  • Shan Jiang
  • Satoru Ono
  • Ira Mellman

[edit] Protocols

[edit] References

[edit] Links

GEO Accession for this experiment: GSE9241. (Public on Oct 06 2007)

PubMed abstract: 17936032

RAW data: tar file.

[edit] Analysis

Gel Plots

Before Normalization

After Normalization & Cleaning

[edit] Samples/Quality Control

Sample Date Scanned Source Link Probe Variance Data Artifact Mask Quality Score
DC_1_CT0hr 07/03/02 12:54:18 GSM234706 Probe variance for DC_1_CT0hr Artifact mask for DC_1_CT0hr 97.7717
0.28 %
98.75
DC_2_CT36hr 07/03/02 13:05:41 GSM234708 Probe variance for DC_2_CT36hr Artifact mask for DC_2_CT36hr 96.9866
4.03 %
96.48
DC_3_CD1hr 07/03/02 13:17:31 GSM234710 Probe variance for DC_3_CD1hr Artifact mask for DC_3_CD1hr 97.839
0.7 %
98.57
DC_4_CD3hr 07/03/02 13:39:47 GSM234712 Probe variance for DC_4_CD3hr Artifact mask for DC_4_CD3hr 97.6335
1.28 %
98.18
DC_5_CD6hr 07/03/02 16:51:43 GSM234713 Probe variance for DC_5_CD6hr Artifact mask for DC_5_CD6hr 98.1909
0.3 %
98.94
DC_6_CD12hr 07/03/02 17:02:34 GSM234716 Probe variance for DC_6_CD12hr Artifact mask for DC_6_CD12hr 97.9666
2.54%
97.71
DC_7_CD18hr 07/03/02 16:32:04 GSM234717 Probe variance for DC_7_CD18hr Artifact mask for DC_7_CD18hr 97.3437
3.45 %
96.95
DC_8_CD36hr 07/03/02 17:14:16 GSM234718 Probe variance for DC_8_CD36hr Artifact mask for DC_8_CD36hr 97.9057
0.33 %
98.79
DC_9_B1hr 07/03/02 13:59:36 GSM234719 Probe variance for DC_9_B1hr Artifact mask for DC_9_B1hr 97.8258
0.33 %
98.75
DC_10_B3hr 07/03/02 14:11:42 GSM234720 Probe variance for DC_10_B3hr Artifact mask for DC_10_B3hr 97.6001
0.33 %
98.63
DC_11_B6hr 07/03/02 14:38:59 GSM234722 Probe variance for DC_11_B6hr Artifact mask for DC_11_B6hr 97.4165
0.39 %
98.51
DC_12_B12hr 07/03/02 14:26:05 GSM234723 Probe variance for DC_12_B12hr Artifact mask for DC_12_B12hr 96.88
4.55 %
96.16
DC_13_B18hr 07/03/02 17:48:46 GSM234757 Probe variance for DC_13_B18hr Artifact mask for DC_13_B18hr 96.84
2.9 %
96.97
DC_14_B36hr 07/03/02 17:38:16 GSM234758 Probe variance for DC_14_B36hr Artifact mask for DC_14_B36hr 95.56
9.78 %
92.89
DC_15_Ab6hr 07/03/02 17:59:38 GSM234760 Probe variance for DC_15_Ab6hr Artifact mask for DC_15_Ab6hr 97.45
4.24 %
96.61
DC_16_Ab12hr 07/03/02 17:26:59 GSM234761 Probe variance for DC_16_Ab12hr Artifact mask for DC_16_Ab12hr 96.48
2.99 %
96.75
DC_17_Ab36hr 07/03/02 17:26:59 GSM234762 Probe variance for DC_17_Ab36hr Artifact mask for DC_17_Ab36hr 97.9
0.37 %
98.76
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