KATP opposes depolarization of cells in the heart, smooth muscle, and other tissues by permitting the efflux of potassium ions and this efflux is evidently required to prevent unopposed vasoconstriction and insufficiency of coronary artery blood flow triggered by one or more cytokines induced in response to LPS. The cytokine(s) involved must elicit a dysfunctional response in the Kir6.1-deficient environment, and to gain further insight into the effects of the mutation, we examined the transcriptional status of whole heart, isolated from normal C57BL/6J mice or KcnJ8Md/Md mice, before and after injection of 1 g of LPS
ATP-sensitive potassium channels mediate survival during infection in mammals and insects.
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View SamplesMurine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection.
Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation.
Specimen part
View SamplesMurine Cytomegalovirus (MCMV) infection leads to the activation of various immune cells, including dendritic cells (DCs) and Natural Killer (NK) cells. This activation is partly driven by innate cytokines including IFN-I, which are induced early after infection. The objective was to address the role of different innate cytokines in shaping DC subsets and NK cell responses, in particular the role of cell intrinsic responses to IFN-I.
Differential responses of immune cells to type I interferon contribute to host resistance to viral infection.
Specimen part
View SamplesDendritic cells (DCs) are a complex group of cells which play a critical role in vertebrate immunity. They are subdivided into conventional DC (cDC) subsets (CD11b and CD8alpha in mouse) and plasmacytoid DCs (pDCs). Natural killer cells are innate lymphocytes involved in the recognition and killing of abnormal self cells, including virally infected cells or tumor cells. DCs and NK cells are activated very early upon viral infections and regulate one another. However, the global responses of DC and NK cells early after viral infection in vivo and their molecular regulation are not entirely characterized. The goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of DC and NK cells during a viral infection in vivo, as compared to B lymphocytes, and to investigate the underlying molecular mechanisms
Differential responses of immune cells to type I interferon contribute to host resistance to viral infection.
Sex, Specimen part
View SamplesThe injection of the pathogen-associated molecular pattern Polyinosinic-polycytidylic acid (poly(I:C)) leads to the activation of various immune cells, including dendritic cells (DCs) and Natural Killer (NK) cells. This activation is due to different innate cytokines produced early after injection, in particular IFN-I. The objective of the study was to compare the pattern of expression of IFN-I stimulated genes between DC and NK cells.
Differential responses of immune cells to type I interferon contribute to host resistance to viral infection.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesThis series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. These events occur independtly of type I interferons and of the microlofora, since the same maturation pattern is observed in XCR1+ tDcs from control, Ifnar1-KO and germ-free mice. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesXCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of nave CD8 T cells. This property was reported to be associated to the subset of the XCR1+ DC expressing IL-12b upon ex vivo stimulation for 24 h with a mixture of CpG, IFN-, and GM-CSF (Lin ML et al. Proc Natl Acad Sci USA. 2008. PMID: 18272486). DC found in the steady-state non-lymphoid tissues undergo an homeostatic, tolerogenic, maturation and migrate to the draining lymph nodes to interact with naive autoreactive T cells and induction their peripheral tolerance. In contrast, spleen DC are thought to exist solely in an immature state. The aim of this study was to re-examine heterogeneity within steady state spleen XCR1+ DC, in particular examining whether this population encompass a fraction of mature DCs as assessed through their expression of CCR7 and/or the Il12b gene. Indeed, we show that a small fraction of XCR1+ spleen DC constitutively mature into two distinct but likely successive activation stages characterized as CCR7+ and CCR7+Il12b+ respectively, and correlated with increasing ability to cross-present antigen to nave CD8 T cells. Transcriptomic analysis of the subsets of XCR1+ DC found in steady state spleen unexpectedly showed that their homeostatic maturation was unexpectedly associated with up-regulated of many genes thought to drive pro-inflammatory T-cell responses and previously found to be commonly induced upon maturation of distinct DC subsets in response to stimulation by various microbial-type stimuli (Vu Manh TP et al. Eur J Immunol. 2013. PMID: 23553052). Thus, our results reveal that spleen XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating upon homeostatic, tolerogenic, DC maturation versus microbial-type stimuli-induced, immunogenic, DC maturation.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
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