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| Status |
Public on Jun 30, 2011 |
| Title |
IL13 and CCL2 drive disease in an inflammatory subset of Scleroderma [IL4] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Scleroderma is a lethal and currently irreversible autoimmune disease characterized by widespread tissue fibrosis and vasculopathy. Using cross-species comparative gene expression profiling we show that murine sclerodematous graft-versus-host disease (sclGVHD) approximates an “inflammatory” subset of human scleroderma and that both diseases demonstrate activation of the IL13 cytokine pathway. We report that both host myeloid cells expressing type I and II activated macrophage markers and graft T-cells produce IL13 and that host mice deficient in either IL13 or IL4Ra, an IL13 signal transducer, are protected from disease. This signaling pathway converges on a single gene, CCL2, which is coordinately upregulated in sclGVHD, in the human inflammatory scleroderma subset and in IL13 treated human dermal fibroblasts. Accordingly, treatment with antibodies to CCL2, and its murine homolog CCL12, prevent sclGVHD. Lastly, we provide evidence that IL13 pathway activation in early scleroderma patients correlates with modified Rodnan skin scores (mRSS). These data indicate that an inflammatory subset of scleroderma is driven by IL13 and may benefit from IL13 or CCL2 blockade.
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| Overall design |
sample vs reference. Total RNA isolated from a time course of primary adult dermal fibroblasts treated with 50nM recombinant IL4 over 24 hours
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| Contributor(s) |
Sargent JL, Aliprantis AO, Greenblatt M, Farina G, Lafyatis R, Tsang K, Glimcher L, Whitfield ML |
| Citation(s) |
22245215 |
| |
| Submission date |
Sep 28, 2010 |
| Last update date |
Feb 18, 2020 |
| Contact name |
Jennifer L Sargent |
| E-mail(s) |
jennifer.sargent@gmail.com
|
| Organization name |
Dartmouth Medical School
|
| Department |
Genetics
|
| Lab |
Whitfield
|
| Street address |
Dartmouth College; HB7400
|
| City |
Hanover |
| State/province |
NH |
| ZIP/Postal code |
03755 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE24410 |
IL13 and CCL2 Drive Disease in an Inflammatory Subset of Scleroderma |
|
| Relations |
| BioProject |
PRJNA133469 |
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