Filters
Technology
Platform
GSE21671
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4+ T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4+ T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis.
Publication Title
Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 4000
Description
The balance between tolerogenic and inflammatory responses determines immune homeostasis in the gut. Dysbiosis and a defective host defense against invading intestinal bacteria can shift this balance via bacterial-derived metabolites and trigger chronic inflammation. We show that the short chain fatty acid butyrate modulates monocyte to macrophage differentiation by promoting antimicrobial effector functions. The presence of butyrate modulates antimicrobial activity via a shift in macrophage metabolism and reduction in mTOR activity. This mechanism is furthermore dependent on the inhibitory function of butyrate on histone deacetylase 3 (HDAC3) driving transcription of a set of antimicrobial peptides including calprotectin. The increased antimicrobial activity against several bacterial species is not associated with increased production of conventional cytokines. Butyrate imprints antimicrobial activity of intestinal macrophages in vivo. Our data suggest that commensal bacteria derived butyrate stabilize gut homeostasis by promoting antimicrobial host defense pathways in monocytes that differentiate into intestinal macrophages. Overall design: Paired samples of control and butyrate-treated macrophages prepared from two individuals.
Publication Title
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 4000
Description
GM-CSF positve CD4 cells are found at sites of inflammation. The purpose of this study was to understand their transcriptional profile relative to known Th1 and Th17 subsets. Overall design: Human CD4 T cells were isolated by magnetic negative selection and activated with PMA and ionomycin. A cytokine capture assay was used to isolate CD45RA-positive, cytokine negative, IFN-gamma-single-positive, IL-17A-single-positive, GM-CSF-single positive and IL-17A-GM-CSF-double positive cells.
Publication Title
Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
IL-23 negatively regulates St2 and Gata3 expression in intestinal CD4+ T cells
Publication Title
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray to compare gene expression between CD161++/CD161+/CD161-CD8+ T cells from human cord blood.
Publication Title
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to compare gene expression between healthy human CD161++CD8aa and CD161++CD8ab T cells.
Publication Title
Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutations of STAT3 underlie the autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in non-hematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and non-hematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
Publication Title
A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Weve undertaken a genome-wide approach to identify and test genes in fibroblasts that are both induced upon interaction with basal breast cancer cells in culture and upregulated in stromal cells from primary human breast cancers. Several of the upregulated genes encode secreted growth factors or cytokines. Using RNAi and a co-injection tumorigenicity assay, we determined that the majority of secreted factors selected for functional validation played significant, yet functionally diverse, roles in promoting tumorigenicity. Rather than a single major mediator, these results indicate multiple points of intervention to prevent fibroblasts from supporting basal breast cancer. Additionally, we show that breast cancer subtypes differ markedly in the expression of these and other stromally secreted proteins using data from microdissected stromal samples.
Publication Title
System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.
Sample Metadata Fields
No sample metadata fields
View Samples