Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from control, aged and activated neutrophils in mouse blood

ABSTRACT: Neutrophils provide immune protection against pathogens but also may promote tissue injury in inflammatory diseases. Although neutrophils are generally considered as a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and the replenishment by newly released neutrophils from the bone marrow. We used microarray to globally analyze gene expression in aged neutrophils and characterize the inflammatory programs that are activated during the aging process in the circulation. Control, aged and activated neutrophils were sorted directly from mouse blood for RNA extraction and hybridization on Affymetrix microarrays. We transfused whole blood and harvested donor neutrophils marked by the CD45.1 allele 6h later to derive neutrophils that had truly aged in vivo. Sorted neutrophils were compared to control donor neutrophils that had been transferred for only 10 min. Additionally, we harvested circulating neutrophils from TNF-? treated mice for comparison with neutrophils activated by systemic inflammation.

ORGANISM(S): Mus musculus

SUBMITTER: Dachuan Zhang

PROVIDER: E-GEOD-69886 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Neutrophil ageing is regulated by the microbiome.

Zhang Dachuan D Chen Grace G Manwani Deepa D Mortha Arthur A Xu Chunliang C Faith Jeremiah J JJ Burk Robert D RD Kunisaki Yuya Y Jang Jung-Eun JE Scheiermann Christoph C Merad Miriam M Frenette Paul S PS

Nature 20150916 7570

Blood polymorphonuclear neutrophils provide immune protection against pathogens, but may also promote tissue injury in inflammatory diseases. Although neutrophils are generally considered to be a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and replenishment by newly released neutrophils from the bone marrow. Aged neutrophils upregulate CXCR4, a receptor allowing their clearance in the bon ...[more]

PMID: 26374999

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Project description:Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel antibody transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von-Willebrand-factor A like domain 2) transfer showed clear variability among inbred mouse strains; i.e. severe cutaneous blistering and inflammation in C57Bl/6J, and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57Bl/6J or MRL/MpJ mice showed an impaired ROS release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune-complex activated neutrophils from either C57Bl/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA. We used microarray to differentiate between the molecular response for the immune complex stimulated neutrophils in MRL/MpJ and C57Bl/6J mice To unravel the molecular basis for the different response to immune complex (IC) stimulation between MRL/MpJ and C57Bl/6J mice, the cells were activated using IC, and differential expression using microarray was compared between resting or activated neutrophils from MRL/MpJ or C57Bl/6J mice.

Dataset Information

Expression data from control, aged and activated neutrophils in mouse blood

Publications

Neutrophil ageing is regulated by the microbiome.

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