The Suppressor of cytokine signaling (SOCS) family of negative regulatory proteins are upregulated in response to several cytokines and pathogen-associated molecular patterns (PAMPs), and suppress cellular signaling responses by binding receptor phosphotyrosine residues. Exposure of bone marrow-derived dendritic cells (BMDCs) to 1D8 cells, a murine model of ovarian carcinoma, suppresses their ability to express CD40 and stimulate antigen specific responses in response to PAMPs, and in particular to poly I: C with the upregulated SOCS3 transcript and protein levels. The ectopic expression of SOCS3 in both the macrophage cell line RAW264.7 and BMDCs decreased signaling in response to both poly I:C and IFN. Further, knockdown of SOCS3 transcripts significantly enhanced the responses of RAW264.7 and BMDCs to both poly I: C and IFN. Immunoprecipitation and pull-down studies demonstrate that SOCS3 binds to the IFN receptor TYK2. Since poly I: C triggers autocrine IFN signaling, binding of SOCS3 to TYK2 may thereby suppress the activation of BMDCs by polyI:C and IFN. Thus, elevated levels of SOCS3 in tumor-associated DCs may potentially resist the signals induced by TLR3 ligands and type I interferon to decrease DC activation via binding with IFN receptor TyK2.
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View SamplesZebrafish is ideal model organism to study myelination and demyelination. We could use this model to screen demylination relative genes and provide a new idea for clinic therapy.
Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous system demyelination.
Specimen part
View SamplesLactobacillus NK2 (L.NK2) is a commensal microbe, isolated from the mouse intestinal feces in our lab. To examine the potential role of L. NK2 in the gut immunity, we monocolonized GF mice with L.NK2. And, we conducted a microarray experiment to compare the transcriptomes of GF and L.NK2-colonized mice intestines under the same experimental condition
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Specimen part
View SamplesMyeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. At the epigenetic level, lncRNA play an important role in cell differentiation and function. We identify a novel long non-coding RNA (lncRNA) termed as lnc-mdsc in MDSCs, which may tightly control the development of MDSCs.
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View SamplesMyeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. At the epigenetic level, lncRNA play an important role in cell differentiation and function. We identify a novel long non-coding RNA (lncRNA) termed as lnc-mdsc in MDSCs, which may tightly control the development of MDSCs.
No associated publication
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View SamplesGerm free (GF) and conventionalized (CONV-D) wild-type C57Bl/6 male mice in the CARB-fed, 24h fasted, and 30d trained states; plus GF and CONV-D CARB-fed Ppara-/- mice. CARB-fed indicates a standard polysaccharide-rich mouse chow diet.
No associated publication
Sex, Specimen part
View SamplesSusceptible and Resistant mouse strain, e.g. DBA/2J and C57BL/6J respectively, were inoculated with a highly pathogenic H5N1 influenza A virus (A/Hong Kong/213/2003) for 72 hours.
Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesDisruption of protein folding in the endoplasmic reticulum triggers the Unfolded Protein Response (UPR), a transcriptional and translational control network designed to restore protein homeostasis. Central to the UPR is PERK phosphorylation of the alpha subunit of eIF2 (eIF2~P), which represses global translation coincident with preferential translation of mRNAs, such as ATF4 and CHOP, that serve to implement the UPR transcriptional regulation. In this study, we used sucrose gradient ultracentrifugation and a genome-wide microarray approach to measure changes in mRNA translation during ER stress. Our analysis suggests that translational efficiencies vary across a broad range during ER stress, with the majority of transcripts being either repressed or resistant to eIF2~P, while a notable cohort of key regulators are subject to preferential translation. From this latter group, we identify IBTKa as being subject to both translation and transcriptional induction during eIF2~P in both cell lines and a mouse model of ER stress. Translational regulation of IBTKalpha mRNA involves the stress-induced relief of two inhibitory uORFs in the 5'-leader of the transcript. Depletion of IBTKalpha by shRNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKalpha is a key regulator in determining cell fate during the UPR.
Selective mRNA translation during eIF2 phosphorylation induces expression of IBTKα.
Specimen part
View SamplesAnalysis of gene expression in lungs of C57BL/6J mice that develop chronic airway disease phenotypes after a single Sendai virus infection, compared with mice treated with UV-inactivated virus.
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
Sex, Time
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