Microbial metagenomics of experimental colitis in mice
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PROVIDER: PRJEB22710 | ENA |
REPOSITORIES: ENA
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Project description:To detect the protein expression of Mouse with experimental colitis
2022-02-17 | PXD026228 | Pride
Project description:human gut metagenomics VLP reads
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Project description:Background and Aims: The impact of cigarette smoke on inflammatory bowel disease has been established by a large number of epidemiological, clinical, and preclinical studies. Exposure to cigarette smoke is associated with a higher risk of developing Crohn’s disease but is inversely correlated with the development, disease risks, progression, and relapse rate of ulcerative colitis. Few mechanistic studies have investigated the effect of cigarette smoke on intestinal inflammation and microbial composition. Methods: Three groups of mice were exposed to three different concentrations of cigarette smoke for a total of 4 weeks, including 5 days of dextran sulfate sodium treatment to induce colitis and a 7-day recovery period. A comprehensive and integrated comparative analysis of the global colon transcriptome and microbiome, as well as classical endpoints, was performed. Results: Cigarette smoke exposure significantly decreased the severity induced colitis. Colon transcriptome analysis revealed that cigarette smoke downregulated specific pathways in a concentration-dependent manner, affecting both the inflammatory state and composition of the gut microbiome. Metagenomics analysis demonstrated that cigarette smoke can modulate dextran sulfate sodium-induced dysbiosis of specific bacterial genera, contributing to resolve the inflammation or accelerate recovery. Conclusions: Cigarette smoke alters gut microbial composition and reduces inflammatory responses in a concentration-dependent manner. The present study lays the foundation for investigating potential molecular mechanisms responsible for the attenuation of colitis by cigarette smoke.
2020-03-03 | E-MTAB-7988 | biostudies-arrayexpress
Project description:Inflammatory bowel disease (IBD), comprising Crohn´s disease and Ulcerative colitis, is characterized by chronic relapsing inflammation of the gut. It has been shown that increased proteasomal activity is associated with the expression of immunoproteasomes, which enhances NF-kB activation and thus promotes inflammation in IBD-patients. Here, we investigate whether modulation of the proteasomal activity is a suitable therapeutic approach to limit inflammation in colitis. This concept was tested in two different experimental setups. First, development of dextran sulfate sodium (DSS)-induced colitis was tested in lmp7-/--mice, which lack the essential immunoproteasome-subunit LMP7 or in wildtype-mice treated with the proteasome inhibitor bortezomib. Compared to WT mice, lmp7-/- mice revealed significantly attenuated colitis resulting from reduced NF-kB activation in the absence of LMP7. Further, treatment with bortezomib revealed dose-dependent amelioration of DSS-induced inflammation. In both approaches proteasome modulation limited the infiltration of neutrophils, consequently reducing tissue damage. In summary our experiments demonstrate that modulation of the proteasomal activity is effective in attenuating experimental colitis. In particular, our data suggest that the immunoproteasome-subunit LMP7 is a suitable target for the therapy of IBD.
2010-07-07 | GSE18163 | GEO
Project description:Inflammatory bowel disease (IBD), comprising CrohnM-BM-4s disease and Ulcerative colitis, is characterized by chronic relapsing inflammation of the gut. It has been shown that increased proteasomal activity is associated with the expression of immunoproteasomes, which enhances NF-kB activation and thus promotes inflammation in IBD-patients. Here, we investigate whether modulation of the proteasomal activity is a suitable therapeutic approach to limit inflammation in colitis. This concept was tested in two different experimental setups. First, development of dextran sulfate sodium (DSS)-induced colitis was tested in lmp7-/--mice, which lack the essential immunoproteasome-subunit LMP7 or in wildtype-mice treated with the proteasome inhibitor bortezomib. Compared to WT mice, lmp7-/- mice revealed significantly attenuated colitis resulting from reduced NF-kB activation in the absence of LMP7. Further, treatment with bortezomib revealed dose-dependent amelioration of DSS-induced inflammation. In both approaches proteasome modulation limited the infiltration of neutrophils, consequently reducing tissue damage. In summary our experiments demonstrate that modulation of the proteasomal activity is effective in attenuating experimental colitis. In particular, our data suggest that the immunoproteasome-subunit LMP7 is a suitable target for the therapy of IBD. Microarray experiments were performed as dual-color hybridizations. To compensate for dye-specific effects, a dye-reversal color-swap was applied. Samples of proximal colon were cut longitudinally, washed in PBS, shortly incubated in 4M Guanidinium-isothiocyanat and transferred to TRIzol (Invitrogen).
2010-07-06 | E-GEOD-18163 | biostudies-arrayexpress
Project description:Background & Aims: The complex interactions between diet and the microbiota that influence mucosal inflammation and inflammatory bowel disease are poorly understood. Experimental colitis models provide the opportunity to control and systematically perturb diet and the microbiota in parallel to quantify the contributions between multiple dietary ingredients and the microbiota on host physiology and colitis. Methods: To examine the interplay of diet and the gut microbiota on host health and colitis, we fed over 40 different diets with varied macronutrient sources and concentrations to specific pathogen free or germ free mice either in the context of healthy, unchallenged animals or dextran sodium sulfate colitis model. Results: Diet influenced physiology in both health and colitis across all models, with the concentration of protein and psyllium fiber having the most profound effects. Increasing dietary protein elevated gut microbial density and worsened DSS colitis severity. Depleting gut microbial density by using germ-free animals or antibiotics negated the effect of a high protein diet. Psyllium fiber influenced host physiology and attenuated colitis severity through microbiota-dependent and microbiota-independent mechanisms. Combinatorial perturbations to dietary protein and psyllium fiber in parallel explain most variation in gut microbial density, intestinal permeability, and DSS colitis severity, and changes in one ingredient can be offset by changes in the other. Conclusions: Our results demonstrate the importance of examining complex mixtures of nutrients to understand the role of diet in intestinal inflammation. Keywords: IBD; Diet; Microbiota; Mouse Models; Systems Biology
2017-10-30 | GSE104461 | GEO
Project description:SIRPa agonist antibody treatment ameliorates experimental arthritis and colitis
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Project description:Mutations in the gene encoding the transcription factor AutoImmune REgulator (AIRE) are responsible for the ‘Autoimmune PolyEndocrinopathy Candidiasis Ecodermal Dystrophy’ syndrome. AIRE directs expression of tissue restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE-deficiency leads to impaired deletion of autospecific T cell precursors. However, a potential role for AIRE in the function of regulatory T cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8+CD28low phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. We here show that CD8+CD28low Treg from AIRE-deficient mice are transcriptionally and phenotypically normal, exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T cell population.
2011-06-22 | GSE30129 | GEO
Project description:We engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity in vivo. VLPs encapsulating TLR7 agonists were decorated with a synthetic mannose-derived ligand (VLP-Man-OvaI/II) that selectively engages the lectin DC-SIGN. Lectin-TLR7 dual engagement induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand (VLP-PE-OvaI/II) failed to promote DC-mediated cellular responses. We performed bulk RNA-seq experiments on moDCs treated with VLP-Man-OvaI/II and VLP-PE-OvaI/II or unstimulated control moDCs. A total of 486 genes were differentially expressed after treatment with VLP-Man-OvaI/II vs. VLP-PE-OvaI/II (log2FC >1.5 and p<0.05). The significantly upregulated genes included CXCL1, CXCL5, ISG15, IL6, CCL4, ISG20, and SOCS3, all of which are implicated in the TLR7 downstream signaling pathway, suggesting a higher extent of TLR7 activation with the VLP-Man-OvaI/II. Gene set enrichment analysis (GSEA) between VLP-Man-OvaI/II- and VLP-PE-OvaI/II-treated moDCs revealed that hallmark DC activation pathways were also upregulated in VLP-Man-OvaI/II-treated DCs, including pathways related to IFN-a, IFN-g, and TNF-a signaling via nuclear factor-κB (NF-kB). These data give insight into how lectin binding with glycan-costumed VLPs can be employed to reprogram immunity.
2024-09-06 | GSE251818 | GEO
Project description:Human papilloma (HPV) virus-like particle (VLP) vaccines were recently licensed. Though neutralizing antibody titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMC from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization. Vaccination with HPV-16 L1 VLP was associated with modulation of genes involved in the inflammatory/defense response, cytokine, interferon and cell cycle pathways in VLP-stimulated PBMC. In addition, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with the microarray data was seen for over two-thirds of these probesets. Up-regulation of immune/defense response genes by VLP, in particular interferon-induced genes was observed in PBMC collected prior to vaccination, with many of these genes being further induced following vaccination. In conclusion, we used gene expression profiling to identify important innate and adaptive response related- genes induced by vaccination with HPV VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials. Experiment Overall Design: Microarrays (Affymetrix Human Focus) were used to compare the gene expression signature in PBMCs stimulated for 3 days with media alone, Sf9/baculovirus insect cell lysate, and HPV-16 L1 VLP expressed from baculovirus-infected Sf9 insect cells from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization (2 months after the initial immunization. Post-vaccination baculovirus sample for Pt078 and pre-vaccination baculovirus sample for Pt082 failed QC.
2008-11-22 | E-GEOD-13587 | biostudies-arrayexpress