Filters
Technology
Platform
GSE76757
Homo sapiens
6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
assess the efficacy of Pimasertib to characterize its mechanism of action
Publication Title
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including Inflammatory Bowel Diseases by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong co-stimulation of these TH subsets particularly of mucosal CCR9+ T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. Here, we investigated the function of TL1A on human TH17 cells. TL1A together with TGF- IL-6, and IL-23 enhanced the secretion of IL-17 and IFN- from human CD4+ memory T cells. TL1A induced the expression of the transcription factors BATF and T-bet that correlated with the secretion of IL-17 and IFN-. In contrast, TL1A alone induced high levels of IL-22 in memory CD4+ T cells and committed TH17 cells. However, TL1A did not enhance expression of IL-17A in TH17 cells. Expression of the transcription factor aryl hydrocarbon receptor that regulates expression of IL-22 was not affected by TL1A. We performed transcriptome analysis of TH17 cells to determine genes that are transcriptionally regulated by TL1A. transcriptome analysis revealed increased expression of IL-9 in response to TL1A.
Publication Title
The TNF family member TL1A induces IL-22 secretion in committed human T<sub>h</sub>17 cells via IL-9 induction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
Illumina HiSeq 2500
Description
Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A in linking tissue homeostasis and intestinal inflammation is not known. Here, using cell-specific genetic deletion models, we report an essential role for CX3CR1+ mononuclear phagocyte (MNP)-derived TL1A, which is induced by adherent IBD-associated microbiota, in regulating group 3 innate lymphoid cell (ILC3) production of IL-22 and mucosal healing in acute colitis. However, in contrast to this protective role in acute colitis, TL1A-dependent expression of OX40L in MHCII+ ILC3 during colitis leads to co-stimulation of antigen-specific T cells and is required for chronic T cell colitis. These results identify a new role for ILC3 in regulating intestinal T cells and reveal a central role for TL1A in regulating ILC3 barrier immunity during colitis. Overall design: RNA from media- or TL1A-stimulated sorted Lin-CD127+IL23R-GFP+ ILC3s from IL23R-GFP/WT mice
Publication Title
Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Ion Torrent Proton
Description
The TNF family member TL1A (TNFSF15) co-stimulates several T helper subsets and promotes T cell-dependent models of inflammatory diseases, including inflammatory bowel diseases (IBD) and allergic lung disease. TL1A polymorphisms confer susceptibility to IBD and have been associated with disease severity. In this study, we identified TL1A as a strong inducer of TH9 cell differentiation in vitro. Mechanistically, TL1A induced NF-?B signaling and down-stream STAT6 activation and facilitated cooperative binding of BATF, BATF3, and IRF4 to the Il9 promoter. In vivo, utilizing an adoptive T cell transfer model we demonstrated that TL1A promoted IL-9-dependent, TH9 cell-induced intestinal and lung inflammation and blocking anti-IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role for IL-9 in TL1A-induced mucosal inflammation. Overall design: 4 samples (2x2)
Publication Title
A role for BATF3 in T<sub>H</sub>9 differentiation and T-cell-driven mucosal pathologies.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Humoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Publication Title
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Publication Title
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IEC). IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response which protects from small intestinal inflammation. IEC ER stress causes expansion and activation of peritoneal B1b cells independent of microbiota and T cells that culminates in increased lamina propria and luminal IgA. Xbp1dIEC mice exhibit IEC ER stress by conditional deletion of X-box-binding protein 1 (XBP1). Here we examine single-cell transcriptomes of peritoneal cavity cells of germ-free Xbp1dIEC mice (KO) compared to littermate controls (WT). Overall design: Single-cell gene expression profiles of peritoneal cavity cells of 10-week-old germ-free Xbp1dIEC and WT mice were generated using a droplet-based system (10X Genomics Chromium).
Publication Title
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples