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Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation [reanalyzed samples]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Marc DALOD

PROVIDER: E-GEOD-71170 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.

Ardouin Laurence L Luche Hervé H Chelbi Rabie R Carpentier Sabrina S Shawket Alaa A Montanana Sanchis Frédéric F Santa Maria Camille C Grenot Pierre P Alexandre Yannick Y Grégoire Claude C Fries Anissa A Vu Manh Thien-Phong TP Tamoutounour Samira S Crozat Karine K Tomasello Elena E Jorquera Audrey A Fossum Even E Bogen Bjarne B Azukizawa Hiroaki H Bajenoff Marc M Henri Sandrine S Dalod Marc M Malissen Bernard B

Immunity 20160801 2

Dendritic cells (DCs) are instrumental in the initiation of T cell responses, but how thymic and peripheral tolerogenic DCs differ globally from Toll-like receptor (TLR)-induced immunogenic DCs remains unclear. Here, we show that thymic XCR1(+) DCs undergo a high rate of maturation, accompanied by profound gene-expression changes that are essential for central tolerance and also happen in germ-free mice. Those changes largely overlap those occurring during tolerogenic and, more unexpectedly, TLR ...[more]

PMID: 27533013

Similar Datasets

Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation

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

Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-08-22 | GSE71171 | GEO

Broad and largely overlapping molecular changes arise in thymic and peripheral XCR1+ dendritic cells upon tolerogenic and immunogenic maturation [reanalyzed samples]

Project description:This series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907.

2016-08-22 | GSE71170 | GEO

Immunogenic and tolerogenic cell death.

Project description:The immune system is routinely exposed to dead cells during normal cell turnover, injury and infection. Mechanisms must exist to discriminate between different forms of cell death to correctly eliminate pathogens and promote healing while avoiding responses to self, which can result in autoimmunity. However, an effective immune response against host tissue is often needed to eliminate tumours following treatment with chemotherapeutic agents that trigger tumour cell death. Consequently, a central problem in immunology is to understand how the immune system determines whether cell death is immunogenic, tolerogenic or 'silent'.

| S-EPMC2818721 | biostudies-literature

Tolerogenic XCR1+ dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis.

Project description:BACKGROUND:Spondyloarthritis (SpA) is a chronic inflammatory disease affecting primarily axial and peripheral joints and sometimes also extra-articular organs, such as the gut. Rats transgenic for HLA-B27 and human ?2-microglobulin (B27-Tg rat) develop clinical manifestations resembling human disease. In this model, it has been shown that CD103+ conventional dendritic cells (cDCs) exhibited altered functions, likely promoting SpA development. CD4- cDC subpopulation expressing XCR1, a chemokine receptor involved in their migration, have been described to be tolerogenic in steady state. Thus, in this study, we wished to examine the fate of XCR1+ cDCs in this animal model of SpA. METHODS:cDC populations were isolated from the spleen, mesenteric lymph nodes (MLN), and colonic lamina propria from B27-TG and control nontransgenic (NTG) and/or HLA-B7 transgenic rats after collagenase digestion and density gradient and characterized with flow cytometry or real-time PCR. Migration of cDCs from intestinal mucosa to MLN was assessed, using TLR-7 stimulation with Resiquimod. RESULTS:We observed a reduced frequency of cCD4- DCs in B27-Tg rats, as compared to control rats. Furthermore, such decrease was not due to excessive death of CD4- cDCs in B27-Tg rats. Interestingly, we observed a decrease frequency of the XCR1+ subpopulation among CD4- cDCs in the spleen, MLN, and lamina propria from B27-Tg rats. Finally, after TLR-7 stimulation, the migration of XCR1+ cDCs to MLN was proportionally reduced in B27-Tg rats. CONCLUSION:Our results demonstrate for the first time a decreased proportion of the tolerogenic XCR1+ cDC subpopulation in SpA target organs in B27-Tg rat, which may affect the maintenance of self-tolerance and control of inflammation.

| S-EPMC6360689 | biostudies-literature

Transcriptional determinants of tolerogenic and immunogenic states during dendritic cell maturation.

Project description:Dendritic cells (DCs) promote either tolerogenic or immunogenic T cell responses, the latter upon sensing microbes. Using an in vitro system, we analyzed transcriptional determinants that enable mature DCs to direct these opposing T cell outcomes. In the absence of microbial products, the transcription factor interferon regulatory factor 4 (IRF4) promotes regulatory T cell (Treg) generation by enhancing expression of genes required for antigen presentation along with those for T cell tolerance. IRF4-deficient DCs were impaired for Treg generation in vivo. When exposed to microbial stimuli, DCs activated nuclear factor (NF)-κB, which induced expression of a proinflammatory cytokine module that, along with the antigen presentation module, promoted the generation of effector T cells. NF-κB was, however, dispensable for Treg development. Chromatin profiling revealed transcriptional motifs associated with the divergent DC programs. Thus, DCs modulate their ability to prime tolerogenic or immunogenic T cells by expressing a core antigen presentation module that is overlaid by distinctive regulatory modules to promote either tolerance or immunity.

| S-EPMC5350508 | biostudies-literature

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation.

Project description:Phagocytosis of dying cells is a major homeostatic process that represents the final stage of cell death in a tissue context. Under basal conditions, in a diseased tissue (such as cancer) or after treatment with cytotoxic therapies (such as anticancer therapies), phagocytosis has a major role in avoiding toxic accumulation of cellular corpses. Recognition and phagocytosis of dying cancer cells dictate the eventual immunological consequences (i.e., tolerogenic, inflammatory or immunogenic) depending on a series of factors, including the type of 'eat me' signals. Homeostatic clearance of dying cancer cells (i.e., tolerogenic phagocytosis) tends to facilitate pro-tumorigenic processes and actively suppress antitumour immunity. Conversely, cancer cells killed by immunogenic anticancer therapies may stimulate non-homeostatic clearance by antigen-presenting cells and drive cancer antigen-directed immunity. On the other hand, (a general) inflammatory clearance of dying cancer cells could have pro-tumorigenic or antitumorigenic consequences depending on the context. Interestingly, the immunosuppressive consequences that accompany tolerogenic phagocytosis can be reversed through immune-checkpoint therapies. In the present review, we discuss the pivotal role of phagocytosis in regulating responses to anticancer therapy. We give particular attention to the role of phagocytosis following treatment with immunogenic or immune-checkpoint therapies, the clinical prognostic and predictive significance of phagocytic signals for cancer patients and the therapeutic strategies that can be employed for direct targeting of phagocytic determinants.

| S-EPMC4987738 | biostudies-literature

Thymic XCR1+ dendritic cells undergo a functional maturation fundamentally similar to that of peripheral tolerogenic XCR1+ dendritic cells

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

Thymic XCR1+ dendritic cells undergo a functional maturation fundamentally similar to that of peripheral tolerogenic XCR1+ dendritic cells

2016-08-22 | E-GEOD-71166 | biostudies-arrayexpress

Role of the immunogenic and tolerogenic subsets of dendritic cells in multiple sclerosis.

Project description:Multiple sclerosis (MS) is an immune-mediated disorder in the central nervous system (CNS) characterized by inflammation and demyelination as well as axonal and neuronal degeneration. So far effective therapies to reverse the disease are still lacking; most therapeutic drugs can only ameliorate the symptoms or reduce the frequency of relapse. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are key players in both mediating immune responses and inducing immune tolerance. Increasing evidence indicates that DCs contribute to the pathogenesis of MS and might provide an avenue for therapeutic intervention. Here, we summarize the immunogenic and tolerogenic roles of DCs in MS and review medicinal drugs that may affect functions of DCs and have been applied in clinic for MS treatment. We also describe potential therapeutic molecules that can target DCs by inducing anti-inflammatory cytokines and inhibiting proinflammatory cytokines in MS.

| S-EPMC4325219 | biostudies-literature

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