Mus musculus
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ABSTRACT:
PROVIDER: PRJNA290493 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation
| PRJNA290486 | ENA
Project description:Dendritic 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. DC were isolated from lymphoid organs as previously described (Vremec et al., 2000). DC subsets were sorted by flow cytometry according to the marker combinations described in the âcharacteristics: phenotypeâ field for each sample.
2016-08-22 | E-GEOD-71166 | biostudies-arrayexpress
Project description:Dendritic 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. DC were isolated from thymus organ as previously described (Luche et al., Eur J Immunol. 2011;41:2165-75.PMID: 21630253), from B6 SPF control, B6 germ-free and Ifnar1-KO mice. DC subsets were sorted by flow cytometry according to the marker combinations described in the Sample records' phenotype field.
2016-08-22 | E-GEOD-78171 | biostudies-arrayexpress
Project description:Dendritic 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.
2016-08-22 | GSE71166 | GEO
Project description:Dendritic 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.
2016-08-22 | GSE78171 | GEO
Project description:Thymic XCR1+ dendritic cells undergo a functional maturation fundamentally similar to that of peripheral tolerogenic XCR1+ dendritic cells
| PRJNA290489 | ENA
Project description:XCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of naïve 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-γ, 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 naïve 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. DC were isolated from the spleen of untreated Il12b-EYFP reporter mice (Reinhardt RL et al. J Immunol. 2006. PMID:16849470) mice as previously described (Robbins SH et al. Genome Biol. 2008. PMID: 18218067; Baranek T et al. Cell Host Microbe. 2012. PMID: 23084923). DC subsets were sorted by flow cytometry according to the marker combinations described in the âcharacteristics: phenotypeâ field for each sample.
2016-08-22 | E-GEOD-71167 | biostudies-arrayexpress
Project description:XCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of naïve 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-γ, 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 naïve 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.
2016-08-22 | GSE71167 | GEO
Project description:Previously we had shown in a mouse model of bronchial asthma that thrombomodulin (TM; CD141; BDCA3) can convert immunogenic conventional dendritic cells into tolerogenic dendritic cells while inducing its own expression on the cell surface. Thrombomodulin+ dendritic cells are tolerogenic while thrombomodulin- dendritic cells are pro-inflammatory and immunogenic. Here we hypothesized that thrombomodulin treatment of dendritic cells would modulate inflammatory gene expression. Murine bone marrow derived dendritic cells were treated with soluble thrombomodulin and expression of surface markers was determined. Treatment with thrombomodulin reduces the expression of maturation markers and increases the expression of TM on the DC surface. Thrombomodulin treated and control dendritic cells were sorted into thrombomodulin+ and thrombomodulin- dendritic cells before their mRNA was analyzed by microarray. mRNAs encoding pro-inflammatory genes and dendritic cells maturation markers were reduced while cell cycle genes were increased in thrombomodulin-treated and thrombomodulin+ dendritic cells compared to control dendritic cells and thrombomodulin- dendritic cells. We compared the effects on global gene expression of treating dendritic cells with soulble thrombomodulin to no treatment, and dendritic cells separated into thrombomodulin+ and thrombomodulin- dendritic cell subsets.
2014-12-31 | GSE45652 | GEO
Project description:Depending on how an antigen is perceived, dendritic cells (DCs) mature in an immunogenic or tolerogenic manner, safeguarding the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well characterized, the signals driving tolerogenic maturation in homeostasis are still poorly understood. Here we demonstrate that engulfment of apoptotic cells triggers homeostatic maturation of conventional cDC1s in the spleen. This process can be modeled by engulfment of empty, non-adjuvanted lipid nanoparticles (LNPs), is marked by intracellular accumulation of cholesterol, and highly unique to type 1 DCs. Engulfment of apoptotic cells or cholesterol-rich LNPs leads to activation of the LXR pathway driving cellular cholesterol efflux and repression of immunogenic genes. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs represses the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell immunity. These data demonstrate how DCs exploit the conserved cellular cholesterol efflux pathway to regulate induction of tolerance or immunity and reveal that administration of non-adjuvanted cholesterol-rich LNPs is a powerful platform for inducing tolerogenic DC maturation.
2023-03-30 | GSE228523 | GEO