Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of mouse spleen XCR1+ DC at steady state, 3 hours after polyI:C or 12 hours after STAg i.v. injection

ABSTRACT: The goal of this experiment was to use global gene expression profiling to compare the global genetic reprogramming of spleen XCR1+ DC upon in vivo stimulation with a viral-type ligand, polyI:C which strongly induces type I interferons, versus with a ligand derived from an intracellular parasite which strongly induces IFN-g. DC were isolated as previously described (Robbins SH et al. Genome Biol. 2008. PMID: 18218067; Baranek T et al. Cell Host Microbe. 2012. PMID: 23084923), from the spleens of wild-type C57BL/6 mice 12 hours after i.v. injection of 20Âµg of STAg. DC subsets were sorted by flow cytometry according to the marker combinations described in the âcharacteristics: phenotypeâ field for each sample. The data for spleen XCR1+ DC isolated from untreated control animals or from mice that had been injected i.v. with 100Âµg polyI:C 3 hours before organ harvest have been previously published and are available in the GEO database GSE39556 series. The complete dataset representing: (1) the Samples corresponding to STAg stimulation and (2) the untreated control Samples and the Samples corresponding to polyI:C stimulation from Series GSE39556 (re-processed using RMA), is linked below as a supplementary file.

ORGANISM(S): Mus musculus

SUBMITTER: Marc DALOD

PROVIDER: E-GEOD-71168 | 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.

Dataset Information

Gene expression profiling of mouse spleen XCR1+ DC at steady state, 3 hours after polyI:C or 12 hours after STAg i.v. injection

Publications

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

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