Peyers patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution,
Innate and adaptive immune functions of peyer's patch monocyte-derived cells.
Sex, Age, Specimen part
View SamplesPsoriasis is a chronic inflammatory skin disease of unknown etiology. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Topical application of Imiquimod, a Toll-like receptor 7 agonist, induces psoriasis in patients and psoriasiform inflammation in mice. We showed that daily application of Imiquimod for 14 days recapitulated both the initiation and the maintenance phase of psoriasis. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs and macrophages in the skin, we characterized their dynamics during both phases of psoriasis. During the initiation phase, neutrophils infiltrated the epidermis whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the maintenance phase, LCs and macrophage numbers increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by transcriptional analysis. Continuous depletion of LCs during the course of Imiquimod treatment aggravated chronic psoriatic symptoms as documented by an increased influx of neutrophils and a stronger inflammation. Therefore, by developing a mouse model that mimics the human disease more accurately, we established that LCs play a negative regulatory role during the maintenance phase of psoriasis.
Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
Specimen part, Treatment
View SamplesIn support of our manuscript investigating the roles of ILCs and T cells in the maintenance of gut hoemostasis, we have performed RNAseq on terminal illeum of mice lacking either all adaptive immune cells (RAG1 -/-), deficient in T cells (TCRalpha -/-), or deficient in T cells but co-housed with wild-type mice and RAG1 -/- mice. Overall design: Tissues from three mice per group were analysed, and the following comparisions were made: RAG1-/- vs. WT C57BL/6 and TCRa-/- co-housed vs TCRa-/- seperately housed. Differential expression genes were identified at 1% FDR using DESeq2.
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.
Subject
View SamplesNumerous CD11b+ myeloid cells are present within the dermis. They are very heterogeneous and can be divided in dermal DCs, tissue monocytes and tissue macrophages. At steady state, only CD11b+ DC migrate from the dermis to the skin draining lymph nodes whereas upon DNFB-induced inflammation, CD11b+ DC as well as dermal monocytes migrated to the lymph nodes. The objective of this study was to use gene expression profiling to rigorously identify the different subsets of dermal CD11b+ myeloid cells at steady state and upon inflammation and to characterize their functional potential.
Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin.
Sex, Age, 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
View SamplesThe goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of spleen XCR1+ DC early after MCMV infection in vivo, using on Affymetrix Mouse Gene 1.0 ST Array.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View Samples