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GSE14386
Homo sapiens
29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
IFN, an effective therapy against relapsing-remitting (RR) multiple sclerosis (MS) is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFN targeting innate immune response and their effects on DC-mediated regulation of T-cell differentiation. We found that IFN1a in-vitro treatment of human monocyte-derived dendritic cells (DCs) induced the expression of TLR7 and the members of its downstream signaling pathway, including myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase (IRAK)4, and TNF receptor-associated factor (TRAF)6, while it inhibited the expression of IL-1R. Using siRNA TLR7 gene silencing, we confirmed that IFN-1a-induced changes in MyD88, IRAK4 and IL-1R expression were dependent on TLR7. TLR7 expression was also necessary for the IFN-1a-induced inhibition of IL-1 and IL-23, and the induction of IL-27 secretion by DCs. Supernatant (SN) transfer experiments confirmed that IFN-1a-induced changes in DCs cytokine secretion inhibit Th17 cell differentiation as evidenced by the inhibition of retinoic acid-related orphan nuclear hormone receptor C (RORC) and IL-17A gene expression and IL-17A secretion. Our study has identified a novel therapeutic mechanism of IFN1a, that selectively targets the autoimmune response in MS.
Publication Title
IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma.
Publication Title
Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated the biological features of FL and their relationship to patients outcome. Gene expression analysis was carried out on diagnosis biopsies from 148 follicular lymphoma patients enrolled in the PRIMA clinical trial. We developed a gene expression-based predictor of progression-free survival (PFS) in high-tumour burden FL patients and we analysed gene-expression signatures reflecting different aspects of tumour biology for their association with outcome. proposition SH: We investigated the biological features of FL and their relationship to patients outcome. Gene expression analysis was carried out on diagnosis biopsies from 148 follicular lymphoma patients enrolled in the PRIMA clinical trial. We developed a gene expression-based predictor of progression-free survival (PFS) in high-tumour burden FL patients and we analysed gene-expression signatures reflecting different aspects of tumour biology for their association with outcome.
Publication Title
A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts.
Sample Metadata Fields
Sex, Specimen part
View Samples