Robust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the downstream mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs.
Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway.
Sex, Specimen part
View SamplesDendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) and compared it to splenic DCs (CD11c+ DC), from mice.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View SamplesDendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) from mice.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View SamplesDendritic cells (DCs) play a vital role in innate immunity. Transcriptome of DCs isolated from mouse spleen was obtained and deposited here.
Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part, Cell line
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesAnalysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level.
Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.
Specimen part
View SamplesA congenic mouse line was constructed by introgressing a C3H chromosome 9 region harboring Ath29 into the C57BL/6 apoE-deficient background. RNA was extracted from aorta using a QIAGEN kit . Total RNA was pooled in an equal amount from 3 mice for each group. Standard Affymetrix procedures were performed using 8ug of total RNA.
Characterization of Ath29, a major mouse atherosclerosis susceptibility locus, and identification of Rcn2 as a novel regulator of cytokine expression.
Disease, Disease stage
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
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