Transcriptional profiling of bladder carcinoma T24 cells following CD40 activation by membrane-bound CD40L (mCD40L) compared to soluble CD40L (sCD40L)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE98891 | GEO | 2020/01/24
REPOSITORIES: GEO
Similar Datasets
Project description:Atherosclerosis, the underlying vascular cause of cardiovascular disease, has a strong inflammatory component. The co-stimulatory CD40-CD40 ligand (CD40L) signaling axis is a pivotal regulator of immune responses in atherosclerosis. However, therapeutic long-term inhibition of CD40L will severely compromise the immune system making it a non-viable treatment option. To circumvent this issue, cell-specific inhibition may present a better approach to target the CD40-CD40L axis. Therefore, we generated T cell and platelet-specific knockout mice for CD40L and apolipoprotein E, which were aged for 28 weeks to study their effects on immune status and atherosclerosis. Here, we show that T cell specific deficiency in CD40L signaling reduced plaque progression through hampered Th1 polarization as well as reduced antigen-dependent proliferation and oxLDL IgM production. DC-specific CD40 deficient mice displayed a similar phenotype. Platelet-specific CD40L deficiency, however, failed to decrease atherosclerosis, but ameliorated atherothrombosis. Together, our results illuminate the divergent cell-specific mechanisms of CD40-CD40L signaling in atherosclerosis, which may lead to advances in targeted therapies.
2021-03-16 | GSE145585 | GEO
Project description:The CD40-CD40L dyad seems to play a prominent role fostering the immune-inflammatory response triggered by endothelial cell (EC)-T cell interaction. To comprehensively delineate the involvement of CD40 (TNFRSF5) in EC activation, we combined RNAi-mediated CD40 knock-down with comparative genome-wide transcriptional profiling of EC in response to T cell. We report the initiation of a profound stress response in ECs upon CD40-CD40L engagement through early up-regulation, among others, of the major pro-inflammatory NFkB and MAPK/SAPK pathways and their associated transcription factors. Moreover, we have identified novel genes regulated through the CD40-CD40L interaction, and pathways previously unrecognized to be induced by CD40 signaling in ECs. Thus, we document a strong down-regulation of endothelial APLN by CD40-CD40L interaction, which could lead to vascular tone dysfunction in atherosclerotic lesions. Conversely, CD40-mediated up-regulation of the viral immune surveillance system, notably TLR3, IFIH1, RIG-I, and RNASEL, establishes a reverse link from adaptive to innate immunity in ECs. Moreover, systematic enrichment analysis substantiates endothelial CD40 involvement in the transcriptional regulation of gene networks associated with adhesion and motility, immunity, cell fate control, hemostasis and metabolism. Our study also highlights the potency and specificity of CD40 siRNA mediated inhibition, and the relevance of CD40 signaling pathways for anti-inflammatory therapeutic intervention. Experiment Overall Design: Time course experiment comparing endothelial gene expression profiling of CD40-silenced versus non-silenced cultured cells using RNA interference. Two independent experiments were performed where HUVECs were siRNA-transfected and co-cultured with Jurkat D1.1 for 4, 10, 16 h and harvested for RNA extraction. Technical dye swap duplicates were performed for each of the two biological replicates in all three time points.
2009-02-21 | E-GEOD-10601 | biostudies-arrayexpress
Project description:The CD40-CD40L dyad seems to play a prominent role fostering the immune-inflammatory response triggered by endothelial cell (EC)-T cell interaction. To comprehensively delineate the involvement of CD40 (TNFRSF5) in EC activation, we combined RNAi-mediated CD40 knock-down with comparative genome-wide transcriptional profiling of EC in response to T cell. We report the initiation of a profound stress response in ECs upon CD40-CD40L engagement through early up-regulation, among others, of the major pro-inflammatory NFkB and MAPK/SAPK pathways and their associated transcription factors. Moreover, we have identified novel genes regulated through the CD40-CD40L interaction, and pathways previously unrecognized to be induced by CD40 signaling in ECs. Thus, we document a strong down-regulation of endothelial APLN by CD40-CD40L interaction, which could lead to vascular tone dysfunction in atherosclerotic lesions. Conversely, CD40-mediated up-regulation of the viral immune surveillance system, notably TLR3, IFIH1, RIG-I, and RNASEL, establishes a reverse link from adaptive to innate immunity in ECs. Moreover, systematic enrichment analysis substantiates endothelial CD40 involvement in the transcriptional regulation of gene networks associated with adhesion and motility, immunity, cell fate control, hemostasis and metabolism. Our study also highlights the potency and specificity of CD40 siRNA mediated inhibition, and the relevance of CD40 signaling pathways for anti-inflammatory therapeutic intervention. Keywords: treated vs. untreated comparison, time course
2009-02-10 | GSE10601 | GEO
Project description:We performed microarray analysis of sCD40L-stimulated iDC to derive a signature of CD40 activation. Human monocytes from normal healthy donors were differentiated to iDCs with GM-CSF and IL4. FACS analysis demonstrated the immature status of these cells, illustrated by low expression of CD80, CD40, and CD86. We confirmed that sCD40L induces the maturation of DCs, characterized by higher expression of CD80, HLA-DR, CD86, CD83 and CD40 and secretion of pro-inflammatory cytokines at 24hr post-stimulation. Cells were harvested at 1, 3 and 24hr post-stimulation for microarray analysis.
2017-06-08 | GSE85544 | GEO
Project description:Difference of DNA methylation and Chromatin accessibility of T24 SP cell and T24 NSP cell
2020-01-30 | GSE130641 | GEO
Project description:Rattus norvegicus Cd40, CD40 molecule [Source:RGD Symbol;Acc:619830], is expressed in 4 baseline experiment(s);
| ENSRNOG00000018488 | ExpressionAtlas
Project description:Rattus norvegicus Cd40, CD40 molecule [Source:RGD Symbol;Acc:619830], is differentially expressed in 22 experiment(s);
| ENSRNOG00000018488 | ExpressionAtlas
Project description:Sus scrofa CD40, CD40 molecule [Source:VGNC Symbol;Acc:VGNC:95545], is differentially expressed in 3 experiment(s);
| ENSSSCG00000035078 | ExpressionAtlas
Project description:Macaca mulatta CD40, CD40 molecule [Source:VGNC Symbol;Acc:VGNC:70703], is expressed in 2 baseline experiment(s);
| ENSMMUG00000003683 | ExpressionAtlas
Project description:Homo sapiens CD40, CD40 molecule [Source:HGNC Symbol;Acc:HGNC:11919], is differentially expressed in 146 experiment(s);
| ENSG00000101017 | ExpressionAtlas