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| Status |
Public on Nov 17, 2012 |
| Title |
TREM-1 is a novel therapeutic target in Psoriasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.
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| Overall design |
Monocytes were isolated by plastic adherence, treated with TLR agonists overnight, washed twice and harvested in RTL-buffer. RNA was extracted and processed for microarray.
3 groups and 3 replicates with a paired structure across replicates
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| Contributor(s) |
Suárez-Fariñas M, Lowes M |
| Citation(s) |
23407402 |
| |
| Submission date |
Nov 15, 2012 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Mayte Suarez-Farinas |
| E-mail(s) |
mayte.suarezfarinas@mssm.edu
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| Organization name |
Mount SinaiSchool of Medicine
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| Street address |
1425 Madison Ave, L2-70C, Box 1077,
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10075 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA181125 |
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