Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Marc DALOD

PROVIDER: E-GEOD-71171 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

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Project description:XCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of naÃ¯ve 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-Î³, 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 naÃ¯ve 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.

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Dataset Information

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

Publications

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

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