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| Status |
Public on Jan 04, 2017 |
| Title |
Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
To identify systemic cytokine patterns in Chronic Graft-versus-Host-Disease (CGVHD), we profiled the gene expression of circulating monocytes. Pathway analysis identified two gene sets that were significantly upregulated across a broad range of patients with inflammatory and sclerotic presentations: (1) genes induced by Type I and Type II IFN, and (2) receptor genes for innate immune responses to cellular damage. Multiple IFN-inducible genes involved in signal transduction, anti-viral function, lymphocyte homeostasis, trafficking, and antigen presentation were increased. Furthermore, upregulation of TLR/NLR/CLR receptor genes for nucleic acids, ribonucleoproteins and annexin implicated response to damaged cells as a source of activation of inflammasomes and induction of Type I IFN.
Serial time courses substantiated a pattern of upregulation of multiple IFN-inducible genes at CGVHD onset, and of decline upon therapy and resolution. Corticosteroid effects could be discriminated from CGVHD gene profiles by assessment of glucocorticoid-inducible genes. Elevated expression of IFN-inducible proteins in plasma and tissue substantiated a role for IFN in lymphocyte trafficking and, through upregulation of BAFF, an involvement of IFN in B cell activation in CGVHD. These results support a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.
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| Overall design |
To identify systemic cytokine patterns in Chronic Graft-versus-Host-Disease (CGVHD), we profiled the gene expression of circulating monocytes
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| Contributor(s) |
Hakim FT, Memon S, Jin P, Imanguli M, Wang H, Rehman N, Yan X, Rose J, Mays JW, Dhamala S, Stroncek D, Gress RE |
| Citation(s) |
27694491 |
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| Submission date |
Aug 22, 2014 |
| Last update date |
Jan 25, 2019 |
| Contact name |
PING JIN |
| E-mail(s) |
PJIN@CC.NIH.GOV
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| Organization name |
CC/DTM/NIH
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| Department |
DTM
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| Lab |
CCE
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| Street address |
9000 ROCKVILLE PIKE
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| City |
BETHESDA |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL10739 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [probe set (exon) version] |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA259225 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60674_RAW.tar |
150.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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