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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 18, 2008 |
| Title |
Expression data from decoy receptor 3-treated monocyte-derived macrophages |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of lineages. DcR3 is capable of promoting angiogenesis, inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice over-expressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics.
Keywords: time-dose response
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| Overall design |
Freshly isolated human monocytes were cultured with DcR3 or control hIgG1 in the presence of M-CSF for 2 days. Data were collected from two independent donors
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| Contributor(s) |
Chang Y, Chen T, Lee C, Yang C, Wang H, Wang C, Hsieh S |
| Citation(s) |
18349319 |
| Submission date |
Mar 17, 2008 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Yung-Chi Chang |
| Organization name |
National Yang-Ming University
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| Department |
Microbiology and Immunology
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| Street address |
155, Sec. 2, Li-Nong St.
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| City |
Taipei |
| ZIP/Postal code |
112 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA107355 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10856_RAW.tar |
32.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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