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accession-icon GSE48338
Tpl2 promotes chemokine/chemokine receptor expression and macrophage migration during acute inflammation
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In autoimmune diseases, accumulation of activated leukocytes correlates with inflammation and disease progression, and therefore, disruption of leukocyte trafficking is an active area of research. The protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Herein, we addressed the contribution of Tpl2 to the regulation of macrophage chemokine and chemokine receptor expression and subsequent migration in vivo using a mouse model of Tpl2 ablation. We found that gene expression of the chemokine ligands CCL2, CCL7, CXCL2, and CXCL3 as well as the chemokine receptors CCR1 and CCR5 were reduced in macrophages from the bone marrow and peritoneal cavities of tpl2-/- mice following stimulation with LPS. LPS stimulation repressed chemokine receptor expression of CCR1, CCR2 and CCR5. Notably, LPS-induced repression of CCR1 and CCR5 was significantly enhanced in Tpl2-deficient macrophages and was observed to be dependent upon Erk activation and independent of PI3K and mTOR signaling. Consistent with alterations in chemokine and chemokine receptor expression, tpl2-/- macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of both chemokine receptors and their ligands and provides further insight into how Tpl2 inhibition may disrupt inflammatory networks in vivo.

Publication Title

Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation.

Sample Metadata Fields

Treatment

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accession-icon GSE40666
Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function
  • organism-icon Mus musculus
  • sample-icon 25 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a)

Description

Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 as compared to STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation.

Publication Title

Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function.

Sample Metadata Fields

Age, Specimen part, Treatment

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accession-icon GSE21671
Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon 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

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accession-icon GSE22105
Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during Helper T Cell Differentiation
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.

Sample Metadata Fields

Specimen part

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accession-icon GSE12839
Expression data from human PBMC samples exposed to IL-12 and paired controls
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

The cytokine interleukin-12 (IL-12) is known to play a central role in adaptive and innate immunity.

Publication Title

Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii.

Sample Metadata Fields

Sex

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accession-icon GSE61037
Sex related differences in murine transcriptional response to TCDD toxicity
  • organism-icon Mus musculus
  • sample-icon 65 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500g/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear.

Publication Title

Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE43959
Diet-Induced Developmental Acceleration Independent of TOR and Insulin in C. elegans
  • organism-icon Caenorhabditis elegans
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix C. elegans Genome Array (celegans)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE57947
Identification of genes associated with breast cancer micrometastatic disease in bone marrow using a Patient Derived Xenograft mouse model
  • organism-icon Mus musculus
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

In this study, using a Patient Derived Xenograft (PDX) system established by transplanting primary tumors from pre-metastatic breast cancer patients we demonstrate that development of distant organ metastases correlates with the presence of Bone Marrow Disseminated Tumor Cells (BM DTCs) in the PDX mice. Comparative gene expression analysis of bone marrow (BM) from tumor bearing PDX mice which developed metastatic disease was carried out with BM from non-tumor bearing controls.

Publication Title

Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.

Sample Metadata Fields

Specimen part

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accession-icon GSE43954
Diet specific expression profiles_MA1
  • organism-icon Caenorhabditis elegans
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix C. elegans Genome Array (celegans)

Description

Analysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, E. coli HT115 and Comamonas DA1877

Publication Title

Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE43953
Diet specific expression profiles_MA2
  • organism-icon Caenorhabditis elegans
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix C. elegans Genome Array (celegans)

Description

Analysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, Comamonas DA1877, and Diluted Comamonas (1:1000 Comamonas DA1877:E. coli OP50)

Publication Title

Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.

Sample Metadata Fields

No sample metadata fields

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
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Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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