Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation
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PROVIDER: PRJNA290486 | ENA |
REPOSITORIES: ENA
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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:This SuperSeries is composed of the SubSeries listed below. 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 'characteristics: phenotype' field for each sample for each individual series. GeneChip Mouse Gene 1.0 ST (GPL6246) and GeneChip Mouse Genome 430 2.0 (GPL1261) DAT files were processed using Affymetrix Gene Chip Operating System to generate .CEL files. Normalization of the raw Affymetrix expression data with Robust Multi-chip Analysis were performed through Bioconductor in the R statistical environment (version 3.0.2) using the oligo package (GPL6246) and the affy, affyPLM and yaqcaffy packages (GPL1261). For genes symbol with several probeSets, the most variant probSet has been selected. The two platforms where merged by the unique genes symbols. Quantile Normalization was applied on the merged expression arrays to generate Matrix 1. PCA analysis revealed a strong platform effect. Partial Least Square (PLS) was performed to remove the platform effect and yield Matrix2 which was used for subsequent analyses. The data matrices contain log2 values.
2016-08-22 | E-GEOD-71171 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-08-22 | GSE71171 | 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. 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:This series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907. DC were isolated from lymphoid organs as previously described (Vremec et al., 2000). Normalized data are available on the SuperSeries record, GSE71171.
2016-08-22 | E-GEOD-71170 | biostudies-arrayexpress
Project description:This series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907.
2016-08-22 | GSE71170 | 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. 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. 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: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:Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation [reanalyzed samples]
| PRJNA290493 | ENA