Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses

ABSTRACT: Intestinal macrophages (IMs) are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters IM programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient (Il10-/- ) mice. We identified chromatin accessibility changes associated with bacterial exposure and IL-10-deficiency in both bone-marrow-derived macrophages (BMMs) and IMs. Surprisingly, Il10-/- IMs adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, when recombinant IL-10 was added to Il10-/- cells, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model in which IL-10-deficiency leads to chromatin alterations that contribute to a loss of IM tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE70517 | GEO | 2016/05/10

SECONDARY ACCESSION(S): PRJNA288935

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

IL-10 from intestinal macrophages prevents excessive innate immune responses to bacteria by limiting IL-23 synthesis

Project description:Innate immune responses must be regulated in the intestine to prevent excessive inflammation. Here, using gene reporter mice, we show that a subset of mouse colonic macrophages constitutively produced the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, which is considered similar to enteropathogenic Escherichia coli infection in humans, macrophage IL-10 was required to prevent intestinal pathology and to promote survival. The synthesis of the proinflammatory cytokine IL-23 was significantly increased in infected mice with a myeloid cell specific deletion of IL-10 and the addition of IL-10 reduced in vitro IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 led to reduced morbidity and mortality in the context of macrophage IL-10 deficiency. Transcriptome analysis indicated that the reporter positive and negative colonic macrophage subsets were highly similar, but the reporter positive cells differed for the expression of CD163, an IL-10 target gene, suggesting an autocrine IL-10 signal, and when obtained from infected mice, they had reduced IL-23p19 mRNA. Interestingly, only transfer of the reporter positive cells could rescue IL-10 deficient infected mice. Therefore, these data indicate a pivotal role for a subset of intestinal macrophages that constitutively produces IL-10, perhaps acting in part in autocrine fashion, in controlling excessive innate immune activation, regulation of IL-23 production, and prevention of tissue damage after an acute bacterial infection in the intestine. Two replicates each of IL10+ and IL10- large intestinal macrophages. Data were normalized with the 'rma' function of the Bioconductor package, along with several GEO (GSM616132, GSM616136, GSM616140, GSM868296, GSM868297, GSM868298) and ArrayExpress (E-MEXP-3216: 04-M2WT, 05-M2WT, 06-M2WT) datasets.

2015-05-12 | E-GEOD-58677 | biostudies-arrayexpress

Gene expression in the colon from IL10 KO mice

Project description:That commensal bacteria can influence intestinal inflammation has been observed using other models of chronic colitis. Loss of IL-10, a major immunosuppressive cytokine, induces spontaneous colitis in mice. The incidence of spontaneous polyp formation in IL-10-deficient mice was also completely eliminated in the absence of STING We used microarrays to evaluate the inflammatory cytokine expression in the colon from IL10 KO mice and IL10/STING KO mice.

2018-02-01 | GSE107810 | GEO

Single-cell RNAseq analysis (10X Genomics Chromium) of refilled lung interstium macrophages on day 4 after depletion

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The IMs in Day 4 post-depletion were compared to the those without depletion. Results showed that refilled IMs had a lower ratio of CD206+ IM vs CD206- subpopulation comparing to IMs without depletion, but they shared high similarity to each other, indicating that the de novo IM population had been established before Day 4 post-depletion.

2023-02-07 | GSE193894 | GEO

Single-cell RNAseq analysis (10X Genomics Chromium) of refilled lung interstium macrophages at the time points of 12h, 24h and 48h after depletion

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. The lung IMs and monocytes from the mice at 12 hours (DT12h), 24 hours (DT24h) and 48 hours (DT48h) after diphtheria toxin (DT)-induced IM depletion were analyzed and compared using single-cell RNA sequencing. A subpopulation was found to be a transit differentiating cells from monocytes to IMs. Transcription factor activity analysis and trajectory showed cMAF and MAFb transcription factors played important roles in monocyte-IM differentiation.

2023-02-07 | GSE193896 | GEO

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Project description:Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects from a 10-year prospective study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as subclonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of genetic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident Ã¢Â€ÂœpseudoantralizedÃ¢Â€Â subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

| EGAS00001007067 | EGA

Control of LPS induced gene expression in bone marrow derived macrophages by the p50/p105 subunit of NF-kB and IL-10

Project description:Bone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).

2011-01-10 | GSE19941 | GEO

Gene expression analysis in proximal and distal colons of Lcn2-/- IL10-/- double knock-out mice.

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

Comparison of de novo refilled to original lung interstitial macrophages by bulk RNA-sequencing

Project description:Lung interstitium macrophages (IMs) are non-alveolar resident tissue macrophages which contribute to the lung homeostasis. These cells were reported to be heterogeneous by our group and other teams, which contains two main distinct subpopulations: CD206+ IMs and CD206- IMs. However, the exact origin of IMs and the transcriptional programs that regulate IM differentiation remains unclear. In recent report, we analyzed the refilled IMs in the course of time after induced IM depletion with single-cell RNA sequencing (10X Genomics Chromium) and bulk RNA sequencing. In this study, the de novo refilled CD206+ and CD206- IMs on Day 14 post-depletion were compared to those without depletion. Alvelar macrophages (AMs) samples were also included in this analysis and served as a reference. Results of clustering and PCA analyses showed high similarity between de novo refilled and original IMs for both CD206+ and CD206- subsets. Only 9 genes were find upregulated in refilled IMs: AA467197, Cd109, Igf2r, Rarb and S100a4.

2023-02-07 | GSE194020 | GEO

Coordinated chemokine expression defines macrophage subsets across tissues [scRNA-seq: mPL]

Project description:Lung-resident macrophages, which include alveolar macrophages and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, here we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Other macrophage types shared specific IM chemokine profiles, while also presenting their own unique chemokine signatures. Depletion of CD206hi IMs in Pf4creR26EYFP+DTR and Pf4creR26EYFPCx3cr1DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture.

2023-03-03 | GSE225665 | GEO

Coordinated chemokine expression defines macrophage subsets across tissues [scRNA-seq: mBAL]

2023-03-03 | GSE225663 | GEO