IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on pro-inflammatory mediator production. Here we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3 and a helicase family co-repressor, SBNO2 (Strawberry notch homolog 2) in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3, and co-stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway induced by IL-10 but not STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 specifically repressed NF-kB-mediated transcription and can physically interact. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10.
Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway.
No sample metadata fields
View SamplesAfter activation, CD4+ helper T (Th) cells differentiate
Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages.
Specimen part
View SamplesDuring an immune response, CD8 T cells fall along a gradient of memory potential, but the regulators of these fate decsisions are not well understood. We utlized Id3-GFP and Id2-YFP reporter mice to elucidate the role of Id3 and Id2 during early CD8 T cell differentiation by gene expression.
The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets.
Sex, Specimen part
View SamplesIn this experiment, we analyzed the gene expression profile of WT and TBK1-deficient splenic DCs by RNA sequencing based on three independent samples. The results revealed significant alterations in the expression of a number of genes, most notably the enhanced expression of a large subset of IFN-responsive genes in the TBK1-deficient DCs. Overall design: Fresh splenic DC mRNA profiles of 8-week old wild type (WT) and TBK1-DKO mice were generated by deep sequencing, in triplicate
The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity.
Specimen part, Cell line, Subject
View Samples2,3,7,8-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.
Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
No sample metadata fields
View SamplesIn 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.
Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.
Specimen part
View SamplesAnalysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, E. coli HT115 and Comamonas DA1877
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
No sample metadata fields
View SamplesAnalysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, Comamonas DA1877, and Diluted Comamonas (1:1000 Comamonas DA1877:E. coli OP50)
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
No sample metadata fields
View Samples2,3,7,8tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 g/kg) in adult male and female C57BL/6Kuo mice.
Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Sex, Specimen part
View Samples