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| Status |
Public on Jul 30, 2014 |
| Title |
Gene expression analysis in the spleen of wild type, Sle1.3 (lupus mice) and Sle1.3 mice haplodeficient for E2-2 (exhibiting non functional pDCs) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antibodies to self-nucleic acids, immune complex deposition and tissue inflammation such as glomerulonephritis. Innate recognition of molecular complexes containing self-DNA and RNA and the ensuing production of type I interferons (IFN) contribute to SLE development. Plasmacytoid dendritic cells (pDCs) have been proposed as a relevant source of pathogenic IFN in SLE; however, their net contribution to the disease remains unclear. We addressed this question using haplodeficiency of the pDC-specific transcription factor E2-2 (Tcf4), which causes a specific impairment of pDC function in otherwise normal animals. We report that Tcf4+/- animals were significantly protected from SLE-like disease caused by the overexpression of the endosomal RNA sensor Tlr7. The protection was also observed after the monoallelic deletion of Tcf4 specifically in the dendritic cell lineage. Furthermore, Tcf4 haplodeficiency in the B6.Sle1.Sle3 multigenic model of SLE ameliorated key disease manifestations including anti-DNA antibody production, immune activation and glomerulonephritis. These results provide genetic evidence that pDCs are critically involved in SLE pathogenesis, confirming their potential utility as therapeutic targets in the disease.
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| Overall design |
Cellluar suspension were obtained from the spleen of wild type, Sle1.3 and Sle1.3/E2-2het mice. 10 million of cells were used to isolate RNA from each sample. After RNA isolation a microarray analysis using the Ambion WT labeling kit was done. Expression was analyzed using Affymetrix Mouse Gene 1.0 ST. 2 Wild type mice, 3 Sle1.3 and 3 Sle1.3/E2-2 het mice were used for the analysis.
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| Contributor(s) |
Sisirak V, Reizis BV, Ganguly D |
| Citation(s) |
25180061 |
| |
| Submission date |
May 06, 2014 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Vanjs Sisirak |
| E-mail(s) |
vs2376@columbia.edu
|
| Phone |
212 342 2936
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| Organization name |
Columbia University
|
| Department |
Microbiology and Immunology
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| Lab |
Reizis Lab
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| Street address |
701 west 168th street
|
| City |
New York City |
| State/province |
NY |
| ZIP/Postal code |
10033 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA246271 |
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