Training of neutrophils in chronic colitis augments atherogenesis [scRNA-seq]
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PROVIDER: PRJNA1089995 | ENA |
REPOSITORIES: ENA
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Project description:Training of neutrophils in chronic colitis augments atherogenesis [scATAC-seq]
| PRJNA1089996 | ENA
Project description:Utilizing a chronic colitis model in Apoe-deficient mice, we identify the crucial role of neutrophils in the development of atherosclerosis. We demonstrate that neutrophils are the first cells to respond in both the circulation and the aorta to the repetitive stimulus of chronic intestinal inflammation and acquire inflammatory, pathogenic phenotype. Single cell RNA-Seq and single cell ATAC-Seq analysis of sorted GMP popu;ation revealed that circulating bone marrow neutrophils from repeated DSS-exposed mice acquire the pathogenic phenotype in the bone marrow which can accelerate vascular inflammation in turn.
2025-03-25 | GSE261993 | GEO
Project description:Utilizing a chronic colitis model in Apoe-deficient mice, we identify the crucial role of neutrophils in the development of atherosclerosis. We demonstrate that neutrophils are the first cells to respond in both the circulation and the aorta to the repetitive stimulus of chronic intestinal inflammation and acquire inflammatory, pathogenic phenotype. Single cell RNA-Seq and single cell ATAC-Seq analysis of sorted GMP popu;ation revealed that circulating bone marrow neutrophils from repeated DSS-exposed mice acquire the pathogenic phenotype in the bone marrow which can accelerate vascular inflammation in turn.
2025-03-25 | GSE261992 | GEO
Project description:Neutrophil accumulation in crypt abscesses is a pathological hallmark of ulcerative colitis. Based on recent evidence that mucosal metabolic changes influence disease outcomes, we hypothesized that transmigrating neutrophils influence the transcriptional profile of intestinal epithelia. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by neutrophil-epithelial crosstalk. Real-time O2 sensing indicated that transmigrating neutrophils rapidly deplete microenvironmental O2 sufficient enough to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). Utilizing HIF reporter mice in a TNBS colitis model, we investigated the relative contribution of neutrophils and the respiratory burst to M-bM-^@M-^\inflammatory hypoxiaM-bM-^@M-^] in vivo. Gp91phox-null mice, which mirror human chronic granulomatous disease, developed accentuated colitis compared to control with exaggerated neutrophil infiltration and diminished inflammatory hypoxia. In conclusion, transcriptional imprinting of host tissue by infiltrating neutrophils modulates the host response to inflammation. Likewise, the respiratory burst contributes fundamentally to localized O2 depletion, resultant microenvironmental hypoxia and effective inflammatory resolution. Two models were employed, direct and indirect. The M-bM-^@M-^\DirectM-bM-^@M-^] migration model entailed establishing a chemotactic gradient (using fMLP) across monolayers of T84 intestinal epithelial cells grown on the underside of permeable supports (3um pore). Neutrophils (PMN) were induced to migrate in the physiologically relevant the physiologically relevant basolateral-to-apical direction. Following migration, T84s were rested in complete media and 2hrs later harvested for RNA isolation. In the Indirect model, PMN were applied to T84s as with the direct model. After migration, conditioned supernatants were collected, cells pelleted and supernatants filtered through 0.2um pore. Conditioned supernatants were transferred to naive T84 monolayers for 2hrs, followed by RNA harvest. Each model was exposed to neutrophils (PMN) or not. All monolayers contained chemotactic peptide fMLP on the apical side. Total of 12 samples, 4 conditions in triplicate: Direct migration without neutrophils (T84 +fMLP -PMN), Direct migration with neutrophils (T84 +fMLP +PMN), Indirect migration without neutrophils (T84 +fMLP -PMN), Indirect migration with neutrophils (T84 +fMLP +PMN)
2012-10-31 | E-GEOD-39681 | biostudies-arrayexpress
Project description:Trained immunity is a long-term memory of innate immune cells, generating an improved response upon re-infection. Shigella is an important human pathogen and inflammatory paradigm for which there is no effective vaccine. Using zebrafish larvae we demonstrate that after Shigella priming neutrophils are more efficient at bacterial clearance. We observe that Shigella-induced protection is non-specific and long-lasting, and is unlike training by BCG and β-glucan. Analysis of histone ChIP-seq on primed neutrophils revealed that Shigella training deposits the active H3K4me3 mark on promoter regions of 1612 genes, significantly changing the epigenetic landscape of neutrophils towards enhanced microbial recognition and mitochondrial ROS production. Finally, we demonstrate that mitochondrial ROS plays a key role in enhanced antimicrobial activity of trained neutrophils. It is envisioned that signals and mechanisms we discover here can be used in other vertebrates, including humans, to suggest new therapeutic strategies involving neutrophils to control bacterial infection.
2023-09-13 | GSE217063 | GEO
Project description:Neutrophil accumulation in crypt abscesses is a pathological hallmark of ulcerative colitis. Based on recent evidence that mucosal metabolic changes influence disease outcomes, we hypothesized that transmigrating neutrophils influence the transcriptional profile of intestinal epithelia. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by neutrophil-epithelial crosstalk. Real-time O2 sensing indicated that transmigrating neutrophils rapidly deplete microenvironmental O2 sufficient enough to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). Utilizing HIF reporter mice in a TNBS colitis model, we investigated the relative contribution of neutrophils and the respiratory burst to “inflammatory hypoxia” in vivo. Gp91phox-null mice, which mirror human chronic granulomatous disease, developed accentuated colitis compared to control with exaggerated neutrophil infiltration and diminished inflammatory hypoxia. In conclusion, transcriptional imprinting of host tissue by infiltrating neutrophils modulates the host response to inflammation. Likewise, the respiratory burst contributes fundamentally to localized O2 depletion, resultant microenvironmental hypoxia and effective inflammatory resolution.
2012-10-31 | GSE39681 | GEO
Project description:Microbiota exposure following DSS-induced colitis promotes Mincle-mediated training of myeloid progenitors
| PRJNA1183750 | ENA
Project description:Macrophage-KLF6 signaling promotes experimental atherogenesis
| PRJNA1194027 | ENA
Project description:Objective The risk of ulcerative colitis (UC)-associated colorectal cancer (CRC) increases with the duration of UC. Oral 5-aminosalicylic acid (5-ASA) formulations are the first-line treatment for mild-to-moderate UC; nevertheless, preventive effect of oral 5-aminosalicylic acid (5-ASA) formulations on UC-associated CRC remains unsolved. We investigated the impact of 5-ASA to colitis-associated neoplasia in C57BL/6J-ApcMin heterozygous (ApcMin/+) mice. Design ApcMin/+ mice exposed to 1.5 w/v% dextran sulfate sodium (DSS) ad libitum for 3 days followed by 25 days of tap water to develop colitis-associated neoplasia. Mice were intracolorectally administrated with 5-ASA to evaluate the effects on the number of tumors. The mechanism of action was presumed by microarray analysis using in vivo samples and was confirmed by in vitro culture of HT-29, a human colorectal adenocarcinoma cell line with supernatant of human primary neutrophils. Results A remission between acute and recurrent episodes of diarrhea, which were ameliorated by 5-ASA treatment were observed in this model. The number of tumors was reduced by continuous 5-ASA administration in this model. This reduction was abolished by withdrawal of 5-ASA in remission period compared to continuous 5-ASA administration. Microarray analysis revealed that neutrophils were involved in the protective mechanism of 5-ASA against proliferation of tumors. Additionally, calprotectin production from human primary neutrophil as activation marker was strongly correlated with proliferation of HT-29.
2019-06-26 | GSE83749 | GEO
Project description:Background: Immune cell populations within the intestinal muscularis propria are poorly resolved during colitis. Maintaining homeostasis in this unique niche is of critical importance, highlighted by the poorer prognosis of inflammatory bowel disease associated with inflammation in the muscularis propria. Methods: This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and DSS-induced colitis. Results: In naïve conditions, transcriptional duality is observed in MMφ with two major supopulations: conventional resident Cx3cr1+ MMφs and Lyve1+ MMφs. During colitis, significant changes occur within the muscularis propria, with increases in B-cells, T-cells, monocytes, neutrophils, and dendritic cells. Unlike in the mucosa, single cell transcriptomics indicates that resident MMφs are retained during colitis and exhibit plasticity toward an inflammatory profile. Lyve1+ MMφs, which express anti-inflammatory marker CD163, are absent during colitis. In contrast, resident Cx3cr1+ MMφs remain during colitis. Conclusions: Our findings provide a resource for understanding the immune system in the muscularis propria niche during colitis and resolve the heterogeneity and origins of proinflammatory MMφs during colitis by demonstrating the plasticity of the persistent MMφ population.
2024-07-31 | GSE237862 | GEO