Transcription profiling of mouse colon from interleukin-10 gene-deficient mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Alan Francis McCulloch
PROVIDER: E-GEOD-17990 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Dietary n-3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient (Il10-/-) mice. Methods: At 35 days of age, 12 weaned Il10-/- and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n-3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. Results: In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed Il10-/- compared to C57 mice. Il10-/- mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in Il10-/- mice. Conclusions: These data indicate that dietary EPA induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the Ppara gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins. Experiment Overall Design: The diet abbreviations EPA, OA, AA and CO used in the sample records Experiment Overall Design: refer to the following : Experiment Overall Design: CO : AIN-76A (control) Experiment Overall Design: OA : AIN-76A (fat-free) + 1% corn oil + 3.7% oleic acid Experiment Overall Design: EPA : AIN-76A (fat-free) + 1% corn oil + 3.7% eicosapentaenoic acid Experiment Overall Design: AA : AIN-76A (fat-free) + 1% corn oil + 3.7% arachidonic acid Experiment Overall Design: Corn oil was supplemented with purified linoleic and alpha-linolenic acid to meet the nutritional requirements of mice for these essential fatty acids. Diets fed for 6 weeks.
2008-10-21 | E-GEOD-12028 | biostudies-arrayexpress
Project description:Using Affymetrix data analysis, important signalling pathways and transcription factors relevant to gut inflammation and anti-inflammatory action of probiotics were identified using the clinically validated probiotic VSL#3 and the IL10-knockout mouse, an animal model for inflammatory bowel disease. VSL#3 increased expression of genes in volved in PPAR signalling and metabolism of xenobiotics and decreased expression of genes involved in immune response/inflammatory response. IL10-knockout (IL10-KO) and wildtype (WT) mice housed under specific pathogen free (SPF) conditions were sacrificed at 24 weeks by cervical dislocation. The study is comprised of two independent Microarray experiments. Microarray experiment1 compares gene expression of IL10-KO and WT colon tissue. For microarray analysis RNA was extracted from the colon tissue of each mouse (WT n=7, IL10-KO n=6). Microarray experiment2 compares gene expression of WT and IL10-KO mice fed with either placebo or probiotic VSL#3. IL10-KO and WT mice were fed with placebo or 1.3x109 cfu of lyophilized VSL#3 bacteria post weaning for 21 weeks. For microarray analysis RNA was extracted from the caecum tissue of each mouse (WT Placebo n=6, IL10-KO Placebo n=6, IL10-KO VSL#3 n=6).
2010-05-15 | E-GEOD-13819 | biostudies-arrayexpress
Project description:Epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are involved in the initiation and maintenance of intestinal inflammation. LMD is a technique that allows the extraction of specific cell types, such as colonic epithelial cells, to analyse gene expression. LMD of colon epithelial cells followed by microarray analysis could be of more value than microarray analysis of intact colon for determining which pathways are active in the colon mucosa in the early and late stages of inflammation due to increased sensitivity to changes in specific cell populations. An experiment was performed using microarray analysis of intact colon samples and microdissected colon epithelial cell samples from Il10-/- and C57BL/6J mice at 6 and 12 weeks of age to study the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of colitis. Results showed that intact colon and colon epithelial cell gene expression profiles were similar in terms of pathways between Il10-/- and C57BL/6J mice at 12 weeks of age and between Il10-/- mice at 12 and 6 weeks of age. More immune-related pathways were identified at 6 weeks of age in epithelial cells than intact colon. This suggests that LMD and targeting of specific cell types may be of particular use when studying the early stages of inflammation before the intestinal morphology is detectably altered, by increasing analysis sensitivity to mucosal gene expression changes. 2x2 factorial with two tissue types analysed. Two strains of mouse (Il10 knockout mouse and the background strain C57BL/6J) were sampled at 2 timepoints (6 and 12 weeks of age) and intact proximal colon and colon epithelium harvested from each mouse (6 mice per group except for group colon epithelium C57 mouse 12 weeks where only 5 samples reached quality control standards).
2013-03-01 | E-GEOD-39859 | biostudies-arrayexpress
Project description:Inflammatory Bowel Disease (IBD) is a term describing a collection of conditions characterised by chronic inflammatory disorder of the gastrointestinal tract involving an inappropriate immune response to commensal microorganisms in a genetically susceptible host. Four kiwifruit extracts, aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (A. deliciosa), have previously demonstrated anti-inflammatory activity using in vitro models of IBD. This study examined whether these kiwifruit extracts had immune modulating effects in vivo against inflammatory processes known to be increased in patients with IBD. KFEs were used as a dietary intervention in Il10-/- mice (an in vivo model of IBD) and the C57BL/6J background strain in a 3 x 2 factorial design. While all Il10-/- mice developed significant colonic inflammation compared to the C57BL/6J mice, this was not affected by the inclusion of KFE in the diet. Whole genome gene and protein expression level profiling indicated that KFEs influenced immune signalling pathways and metabolic processes within the colonic tissue; however, the effects were subtle. In particular, adaptive immune pathways were reduced by three out of four kiwifruit extracts, with greater reduction seen in the C57BL/6J mice. This suggests that while immune-modulating activity was present in vivo, KFEs did not reduce inflammatory processes relevant to IBD. Experimental design. Two experiments were conducted, one using extracts from gold kiwifruit and one using extracts from green kiwifruit. Within each experiment, both Il10-/- and C57 mice were randomly divided into three diet treatment groups, to ive the following 12 treatments: 1) Gold Kiwifruit Experiment, C57BL/6J mice, Control diet (AIN-76A), 2) Gold Kiwifruit Experiment, C57BL/6J mice, Aqueous Kiwifruit Extract Supplemented Diet (AIN-76A + 5% Aqueous KFE) 3) Gold Kiwifruit Experiment, C57BL/6J mice, Ethyl Acetate Kiwifruit Extract Supplemented Diet (AIN-76A + 0.11% Ethyl Acetate KFE) 4) Gold Kiwifruit Experiment, Il10-/- mice, Control diet (AIN-76A), 5) Gold Kiwifruit Experiment, Il10-/- mice, Aqueous Kiwifruit Extract Supplemented Diet (AIN-76A + 5% Aqueous KFE) 6) Gold Kiwifruit Experiment, Il10-/- mice, Ethyl Acetate Kiwifruit Extract Supplemented Diet (AIN-76A + 0.11% Ethyl Acetate KFE) 7) Green Kiwifruit Experiment, C57BL/6J mice, Control diet (AIN-76A), 8) Green Kiwifruit Experiment, C57BL/6J mice, Aqueous Kiwifruit Extract Supplemented Diet (AIN-76A + 5% Aqueous KFE) 9) Green Kiwifruit Experiment, C57BL/6J mice, Ethyl Acetate Kiwifruit Extract Supplemented Diet (AIN-76A + 0.11% Ethyl Acetate KFE) 10) Green Kiwifruit Experiment, Il10-/- mice, Control diet (AIN-76A), 11) Green Kiwifruit Experiment, Il10-/- mice, Aqueous Kiwifruit Extract Supplemented Diet (AIN-76A + 5% Aqueous KFE) 12) Green Kiwifruit Experiment, Il10-/- mice, Ethyl Acetate Kiwifruit Extract Supplemented Diet (AIN-76A + 0.11% Ethyl Acetate KFE) Six biological replicates were analysed from each treatment group, except for groups 3 and 7 where five replicates were analysed due to array quality issues with the sixth replicate. Each replicate contained mRNA from one mouse. A reference design was used, where each slide was hybridised with mRNA from one sample (green channel) and mRNA from a common reference pool (red channel).
2011-03-05 | E-GEOD-27684 | biostudies-arrayexpress
Project description:Maternal IL10 deficiency elevates susceptibility to fetal loss induced by the model Toll-like receptor agonist lipopolysaccharide, but the mechanisms are not well elucidated. Here we show that Il10 null mutant (Il10-/-) mice exhibit altered local T cell responses in pregnancy, exhibiting pronounced hyperplasia in para-aortic lymph nodes draining the uterus with >6-fold increased CD4+ and CD8+ T cells compared with wild-type controls. Amongst these CD4+ cells, Foxp3+ Treg cells were substantially enriched, with 11-fold higher numbers at day 9.5 post coitum (pc). Lymph node hypertrophy in Il10-/- mice was associated with more activated phenotypes in dendritic cells and macrophages, with elevated expression of MHCII, scavenger receptor and CD80. Affymetrix microarray revealed an altered transcriptional profile in Treg cells from pregnant Il10-/- mice, with elevated expression of Ctse (cathepsin E), Il1r1, Il12rb2 and Ifng. In vitro, Il10-/- Treg cells showed reduced steady state Foxp3 expression, and polyclonal stimulation caused greater loss of Foxp3 and reduced capacity to suppress IL17 in CD4+Foxp3- T cells. We conclude that despite a substantially expanded Treg cell pool, diminished stability of Treg cells, increased numbers of effector T cells, and altered phenotypes in dendritic cells and macrophages in pregnancy all potentially confer vulnerability to inflammation-induced fetal loss in Il10-/- mice. These findings suggest a pivotal role for IL10 in facilitating robust immune protection of the fetus from inflammatory challenge and suggest IL10 deficiency could contribute to human gestational disorders where altered T cell responses are implicated. RNA was extracted from CD4+CD25+ lymphocytes isolated from para-aortic LNs of day 9.5 pc pregnant Il10+/+ or Il10-/- mice using miRNeasy Mini Kits (Qiagen Inc., Valencia, CA, USA) according to the manufacturer’s instructions. The concentration and purity of each RNA sample was determined using the Nanodrop Spectrophotometer (ND-1000, Nanodrop Technologies Inc., Wilmington, DE). RNA quality was determined using the RNA 6000 Pico Total RNA Kit (Agilent Technologies, Santa Clara CA) prior to use in microarray experiments. RNA with a RIN>7 was used in this study. For microarray analysis, RNA was pooled (from 2-4 mice per pool) resulting in four biological replicates of CD4+CD25+ cells from both Il10-/- and Il10+/+ mice. Microarray analysis was performed using Affymetrix Mouse Gene 2.0 ST Arrays at the Adelaide Microarray Centre. Total RNA was amplified using the Ovation PicoSL WTA System V2 (Nugen Inc., San Carlos, CA, USA) and MinElute Reaction Cleanup Kit (Qiagen Inc., Valencia, CA, USA), according to the manufacturer’s instructions, to provide 5 ?g of cRNA for each microarray. The microarray data was normalized and analyzed using Partek Genomics Suite (Partek Inc, MO). Raw data from the Affymetrix platform (.cel files) were imported and normalized using RMA background correction, Partek’s own GC content correction, and mean probe summarization.
2015-07-30 | E-GEOD-71494 | biostudies-arrayexpress
Project description:Lcn2 is involved in host defense against pathogens, but the function in intestinal mucosal immunity and inflammation remains largely unknown. Genetic ablation of Lcn2 results in early-onset colitis and spontaneous emergence of right-sided colonic tumors in the setting of IL-10 deficiency (Lcn2-/-;IL10-/- mice). To address whether inflammation or other mechanisms drives the site-specific tumor locations gene expression analyses in proximal versus distal colons of Lcn2-/- IL10-/- mice were performed. Differential expression between distal colon versus cecum and proximal colon samples were analyses using Affymetrix MoGene 2.0 ST arrays on formalin-fixed, paraffin-embedded tissue sections of Lcn2-/-; IL10-/-mice.
2016-03-30 | E-MTAB-4583 | biostudies-arrayexpress
Project description:Inappropriate response to normal intestinal bacteria is involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohnâ??s Disease (CD), ulcerative colitis (UC)) and variations in the host genome may mediate this process. IL-10-/- mice develop CD-like colitis mainly in the colon, in part due to inappropriate responses to normal intestinal bacteria including Enterococcus strains. Comprehensive characterization of changes in gene expression associated with the observed inflammation in the IL-10-/- mouse model has yet to be reported. Our aim was to characterize changes in colonic gene expression in IL-10-/- and C57BL/6J (C57; control) mice resulting from oral bacterial inoculation with 12 Enterococcus faecalis and faecium (EF) strains isolated from calves or poultry, complex intestinal flora (CIF) collected from healthy control mice, or a mixture of the two (EFâ?¢CIF). At 12 weeks of age, total RNA extracted from intact colon was hybridized to Agilent 44k mouse arrays. Lists of differentially expressed genes were generated using linear models for microarray analysis (Bioconductor), and genes clustered using GeneSpring GX and Ingenuity Pathways Analysis software. Intestinal inflammation was increased in IL-10-/- mice as a result of inoculation, with the strongest effect being in the EF and EF.CIF groups; expression of >4,000 gene probes was altered in colon tissue compared with similarly inoculated C57 mice. Genes differentially expressed in IL-10-/- mice as a result of EF or EF.CIF inoculation were associated with the following pathways: inflammatory disease (111 genes differentially expressed), immune response (209 genes), antigen presentation (11 genes, particularly major histocompatability complex Class II), fatty acid metabolism (30 genes) and detoxification (31 genes). Our results suggest that the colonic inflammation in EF and EF.CIF-inoculated IL-10-/- mice is mediated by mechanisms similar to those of human IBD, in particular CD. Example logFC calculation; This example describes the calculation of the fold-change value (logFC) for a single spot (in this case, spot 27222) for a single comparison. This calculation method was applied to generate all of the comparison data shown in the supplementary data files. The comparison in question is for:; colon tissue from C57BL/6J mouse with EF.CIF treatment (represented by duplicate samples GSM307282 (Title: C57BL/6J_Colon_EF.CIF_Rep1_(Pool17)) and GSM307283 (Title: C57BL/6J_Colon_EF.CIF_Rep2_(Pool18)); vs. colon tissue from C57BL/6J mouse under conventional conditions (represented by duplicate samples GSM307270 (Title: C57BL/6J_Colon_Conventional_Rep1_(Pool5)) and GSM307271 (Title: C57BL/6J_Colon_Conventional_Rep2_(Pool6)); Important Note: Limma analysis maps the treatments on each slide to the M values which are by convention always log2(R) - log2(G). Because this experiment is a reference design, with the reference RNA always Cy5 (i.e. red, channel 2) and the treatment sample Cy3 (i.e. green, channel 1), and we are interested in the values of the treatment samples compared with the reference, the M values in the data files are displayed as log2(G) - log2(R); The average expression is what is important here, which is calculated from the normalized M values for the appropriate comparison of interest as follows:; [1] Mean value for Spot 27222, for each treatment:; C57BL/6J mouse, EF.CIF: = mean (0.26363587 (GSM307282), 0.05084283 (GSM307283)) = 0.15723935 C57BL/6J mouse, conventional = mean (1.42951674 (GSM307270),1.15444106 (GSM307271)) = 1.2919789; [2] Calculation of LogFC for the comparison of interest:; The contrast of interest is C57BL/6J: EF.CIF vs Conventional, so by performing a subtraction of these values for the comparison of interest (i.e. (mean for EF.CIF) - (mean for Conventional), the common reference is cancelled out, thus:; C57BL/6J: EF.CIF vs Conventional = 0.15723935 - 1.2919789 = -1.13473955; So, the fold-change value (logFC) for spot 27222 for the comparison in question (C57BL/6J: EF.CIF vs. Conventional) is: -1.13473955 Experiment Overall Design: Animals. Twenty five male IL-10-/- (C57BL/6J background, formal designation B6.129P2-IL-10<tm1Cgn>/J) mice and twenty five male C57BL/6J (C57) control mice were received from The Jackson Laboratory (Bar Harbor, Maine, USA) at approximately five weeks of age. Mice were housed either in pairs or groups of three (5 mice per treatment) in shoebox-style cages containing untreated wood shavings and a plastic tube for environmental enrichment. The animal room was maintained at a temperature of ~22°C and humidity of ~50% with a 12 hour light/dark cycle. All mice had ad libitum access to water, which was refreshed twice a week. An AIN-76A powdered diet was supplied twice a week, with sufficient provided to meet the daily intake of IL-10-/- mice, as determined in a previous feeding trial (data not shown). The diet for all groups was sterilized by gamma irradiation (Schering-Plough, Wellington, New Zealand) to a level required for SPF conditions, to minimize the possibility of bacterial introduction to the SPF group of animals. All mice were weighed three times weekly and carefully monitored for disease symptoms (weight loss, soft faeces and inactivity). Experiment Overall Design: Experimental design. Both IL-10-/- and C57 mice were randomly divided into five treatment groups with five animals per group. Experiment Overall Design: SPF. Housed in Specific Pathogen Free (SPF) conditions (isolator cages supplied with HEPA filtered air (Tecniplast SpA, Buguggiate, Italy)). Experiment Overall Design: C. Maintained under conventional conditions. Experiment Overall Design: EF. Maintained under conventional conditions and orally inoculated (200 microlitres) with a solutions containing 12 pure strains of Enterococcus (1.2 x 10^8 colony forming units (CFU)). Experiment Overall Design: CIF. Maintained under conventional conditions and orally inoculated with conventional intestinal flora (CIF) derived from healthy age-matched C57BL/6 mice which had been raised under conventional conditions. The CIF inoculation protocol was included to better mimic the complete microbiota associated with the mouse gastrointestinal tract. Experiment Overall Design: EFâ?¢CIF. Maintained under conventional conditions and orally inoculated with a combination of the EF and CIF inoculation solutions (6.0 x 10^7 CFU from the EF inoculum). Experiment Overall Design: All mice were euthanised via CO2 asphyxiation and cervical dislocation at 12 weeks of age. Blood was collected from euthanised mice by cardiac puncture. Plasma was separated from red blood cells by centrifugation (2000 g, 10 min, 4 ºC), frozen in liquid nitrogen and stored at - 80 ºC. The intestine was removed, cut open lengthwise and flushed with 0â?¢9 % NaCl to remove digesta residues. The proximal half of the colon was cut in two pieces, one for histological evaluation and other for gene expression studies. Samples of the colon tissue for gene expression analysis were frozen in liquid nitrogen and stored at - 80 ºC. Samples for histological analysis were stored in formalin solution (10 % neutral buffered) at room temperature. Experiment Overall Design: Total RNA was extracted from the colon tissues using Trizol (Invitrogen, Carlsbad, CA, USA) as described by the manufacturer, with a subsequent purification step using RNeasy columns (Qiagen, San Diego, CA, USA). RNA was quantified using a NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA) and RNA quality was examined using a RNA 6000 LabChip Kit and a 2100 Bioanalyser (Agilent Technologies, Palo Alto, CA, USA). Experiment Overall Design: The Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies Inc., Palo Alto, California, USA) was used to synthesize cDNA and fluorescent cRNA. Labelled cRNA was made on the same day for all sample pools, including the reference sample. cDNA was synthesized from 500 ng of purified total RNA from each pool using T7 promotor primer and Moloney Murine Leukemia Virus Reverse Transcriptase according to the manufacturerâ??s protocol. Cy3 (PerkinElmer, Waltham, Massachusetts 02451, USA) was used to label sample groups, while the reference RNA was labeled with Cy5 (PerkinElmer, Waltham, Massachusetts 02451, USA). Experiment Overall Design: HYBRIDIZATION Experiment Overall Design: Microarray hybridization was performed according to a reference design without dye swap. The in situ hybridization kit-plus (Agilent Technologies Inc., Palo Alto, California, USA) was used to hybridize cRNA samples to Agilent Technologies Mouse G4121A - 44k 60mer oligonucleotide arrays. Cy3-labelled cRNA (sample, 0.75 µg) and Cy5-labelled cRNA (reference, 0.75 µg) were hybridised onto the microarray according to the manufacturerâ??s protocol. Following hybridisation, slides were washed in solutions I, II and III (Agilent Technologies, Santa Clara, CA, USA) and air-dried. Experiment Overall Design: SCAN PROTOCOL Experiment Overall Design: Slides were scanned using a GenePix 4200A scanner (Molecular Devices Corporation, Sunnyvale, CA, USA) at a photomultiplier tube (PMT) setting of 450 V. Spot identification and quantification were performed using GenePix 6.0 software (Molecular Devices Corporation, Sunnyvale, CA, USA). Spot identification and quantification was performed using GenePix 6.0 software (Molecular Devices). All slides were individually checked and manually flagged for abnormalities. Experiment Overall Design: DATA PROCESSING Experiment Overall Design: Statistical analysis was performed using linear models for microarray analysis (limma) within the Bioconductor framework. Before analysis, poor quality spots were manually flagged and filtered out. Quality of the microarray data was assessed on diagnostic plots (boxplots and density plots) and spatial images generated from the raw (non-processed) data. All twenty arrays passed these strict criteria and were included in the analyses. Intensity ratio values for all microarray spots were normalized using a within-slide global Locally Weighted Scatterplot Smoothing (Loess) procedure to remove the effect of systematic variation in the microarrays; no background correction was necessary due to homogeneous hybridization. The normalized data from the arrays of each treatment group were averaged. For each comparison, differentially expressed genes were identified using false discovery rate (FDR) control with a threshold of q < 0.05. Data were log transformed before analysis and the mean difference between treatments calculated on this scale, resulting in a log ratio for each probe. The normalized values in the database consist of these log ratios. MA plots of the microarray data were drawn in order to check that there was no dependence of the log ratio on the intensity for any slide. The significance of the log ratio for each probe was determined by calculating one modified t-statistic per probe using an empirical Bayes approach. Experiment Overall Design: The probability values were then corrected for multiple testing using the Benjamini and Hochberg correction, and a false discovery rate (FDR) calculated. Probes that had an FDR of less than 5 % (q<0*05) were considered to be differentially expressed between treatment.
2009-01-14 | E-GEOD-12223 | biostudies-arrayexpress
Project description:To gain a global view of the signaling pathways engaged by EphB receptors in the intestinal epithelium, we analyzed the transcriptional alteraltions after acute inhibition of EphB signaling in vivo. An intravenous injection of ephrin-B2-Fc decreases EphB2 tyrosine phosphorylation and results in a reduction in cell proliferation to a similar extent as in EphB2:EphB3 double null mutant mice. Moreover, cells bevome mislocalized along the crypt-villus axis, as in the EphB2;EphB3 --/-- mice, although this is not apparent until several days after injection. By analysing the transcriptome within the first day after blocking EphB signaling, it is possible to study the effect of blocked EphB signaling without the potential secondary effects caused by distorted cell positioning. Since ephrin-B2-Fc binds exclusively to EphB expressing cells inthe crypts in the intestine, it is possible to assess transcriptional alterations in these cells in response to EphB antagonist in whole preparations of colon.
2009-12-18 | E-TABM-753 | biostudies-arrayexpress
Project description:Transcriptional profiling of mice fed a diet deficient in selenium and folate during weaning and in utero (LL), a diet deficient in selenium and folate during weaning but not in utero (HL), a diet sufficient in selenium and folate during weaning but deficient in utero (LH), and a diet sufficient in selenium and folate during weaning and in utero (HH) 2 colour microarray, reference design. Biological replicates: 6 per treatment group. The reference RNA was extracted from a whole pregnant C57 mouse and foetus. The whole body was homogenised and RNA was extracted using an AllPrep(r) DNA/RNA/Protein mini kit (Qiagen, Cat number 80004).
2015-04-23 | E-GEOD-68179 | biostudies-arrayexpress
Project description:Molecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases. Expression profiling of jejunum, ileum, and colon tissue from germ-free and colonized mice at day 1,2,4,8,16 and 30.
2012-07-10 | E-GEOD-32513 | biostudies-arrayexpress