Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Macrophages in Crohn’s disease creeping fat are predominantly inflammatory and produce calprotectin

ABSTRACT: Crohn’s disease is characterized by transmural inflammation and therefore the mesenteric immune compartment has gained interest. However, its significance in Crohn’s disease is largely unclear. Macrophages are plastic cells that adapt their phenotype to environmental stimuli resulting in inflammatory and regulatory macrophage subsets. Hence, their distribution can reflect the overall nature of an immune infiltrate. We show that mesenteric macrophages contain two populations, characterized as CD11b-high and CD11b-dim. The CD11b-dim population is characterized by expression of regulatory markers CD206, CD200R, CD163, PD-L2, CD32. CD11b-high macrophages display an IFNγ induced signature and produce high levels of calprotectin. CD11b-dim and CD11b-high populations were comparable between Crohn’s disease and other indications in expression pattern, but the CD11b-high population was strongly overrepresented in this patient group.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148233 | GEO | 2021/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn’s Disease Patients

Project description:Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. How-ever, most studies have focused on the colon intestinal mucosa, overlooking the contribution of the colon intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. Therefore, we analyzed and compared the gene and protein expression and dysregulated biological functions in the distinct tissue compartments of mucosa and submucosa/wall of colon resections from CD patients. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand refractory disease elements to achieve transmural healing. We employed a comprehensive multi-omics approach to investi-gate the molecular profiles of the colon mucosa and submucosa/wall compartments in patients with chronic Crohn’s disease. The results revealed similarities and differences in gene and protein ex-pression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

2024-06-23 | PXD050335 | Pride

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn's Disease Patients

Project description:Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. . We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH

2024-03-15 | GSE261086 | GEO

The CD200-CD200R axis promotes squamous cell carcinoma metastasis via regulation of Cathepsin K

Project description:The CD200-CD200R immunoregulatory signaling axis plays an etiological role in the survival and spread of numerous cancers primarily through suppression of anti-tumor immune surveillance. Our previous work outlined a pro-metastatic role for the CD200-CD200R axis in cutaneous squamous cell carcinoma (cSCC) that is independent of direct T cell suppression but modulates the function of infiltrating myeloid cells. To identify effectors of the CD200-CD200R axis important for cSCC metastasis, we conducted RNA-Seq profiling of infiltrating CD11b+Cd200r+ cells isolated from Cd200+ versus Cd200 null cSCCs and identified the cysteine protease Cathepsin K (Ctsk) to be highly upregulated in Cd200+ cSCCs. CD11b+Cd200r+ cells, which expressed phenotypic markers associated with myeloid-derived suppressor cell-like cells and tumor-associated macrophages, were the primary source of Ctsk expression in cSCC. Using a Cd200r+ myeloid cell-cSCC co-culture system, we observed that induction of Ctsk in Cd200r+ tumor-infiltrating cells was dependent on engagement of the CD200-CD200R axis, indicating that Ctsk is a target gene of this pathway in the cSCC tumor microenvironment. Inhibition of Ctsk, but not matrix metalloproteinases (MMPs), significantly blocked cSCC cell migration through collagen gels in vitro. Finally, both targeted Cd200 disruption in tumor cells and Ctsk pharmacological inhibition dramatically reduced cSCC metastasis in vivo. Collectively, our findings identify a novel direct role for Cd200r+ infiltrating myeloid lineages in tumor metastasis and support the conclusion that CD200 stimulates cSCC invasion and metastasis via induction of Ctsk in CD200r+ infiltrating cells.

2021-06-19 | GSE178496 | GEO

Human Kupffer Cell Subsets Defined by CD32

Project description:Human liver myeloid cells are imperfectly defined, but it is broadly agreed that cells of stellate appearance in situ, expressing the markers CD11b and CD68, are the liver’s resident macrophages, termed Kupffer cells. Recent investigations using single cell RNA sequencing and unsupervised clustering algorithms suggest there are two populations of cells with the characteristics of tissue macrophages in human liver. We therefore analyzed dissociated human liver tissue using the markers CD11b and CD68 to define Kupffer cells and found within this population two subsets that differ in their expression of multiple surface markers. These subsets were FACS-sorted based on CD32 expression, and gene expression analysis identified them with human liver myeloid cell subsets defined by two independent single cell RNA sequencing studies. These two subsets differed in the expression of genes associated with T cell activation and immunosuppression, suggesting distinct roles in T cell tolerance.

2020-10-27 | GSE154318 | GEO

RNA-seq analysis of normoxic and hypoxic tumor-associated macrophages

Project description:mRNA expression data in FACS sorted CD11b+ F4/80+ tumor-associated macrophages that are derived from normoxic (as characterized by low GLUT1-expression on the cell membrane) or hypoxic (as characterized by high GLUT1-expression on the cell membrane) area's of Lewis Lung Carcinoma tumors injected subcutaneously in either wild type or REDD1 (DDIT4) knockout mice.

2018-01-01 | E-MTAB-5032 | biostudies-arrayexpress

CD11b restricts alveolar macrophage activation during pneumococcal pneumonia and prevents excessive lung inflammation

Project description:Bacterial lung infections are associated with strong infiltration of CD11b+ myeloid cells, which limit life-threatening disease, but also severely damage lung tissue. In a murine lung infection model with Streptococcus pneumoniae, we found intrinsic upregulation of CD11b on resident alveolar macrophages. Such CD11b expression was associated with transcriptomic and proteomic adaptations by alveolar macrophages, leading to the identification of specific molecules and pathways that depended on CD11b. In the absence of CD11b, the antimicrobial defense of alveolar macrophages was strongly reduced, and the production of neutrophil-recruiting chemokines was more pronounced. Moreover, CD11b expression limited the infection and prevented excessive alveolar damage. In conclusion, our study provides detailed molecular insights into the alveolar macrophage-specific immune response to Streptococcus pneumoniae lung infection and reveals profound CD11b-dependent alterations that are critical for effective antimicrobial immunity, neutrophil recruitment, and prevention of alveolar damage.

2023-10-08 | PXD035269 | Pride

Single-cell RNA seq reveals the transcriptional landscape and heterogeneity of macrophages in murine gut tissues

Project description:CD11b+ cell populations, especially macrophages are highly heterogeneous tissue resident immune cells in both mice and human. Exact subsets and their phenotype remain unknown. We here analyzed gut CD11b+ cell populations using scRNA-seq in normal, inflamed and Nlrc4 deficient mice. There existed twelve CD11b+ cell populations and subsets in SPF mice. These CD11b+ subsets were changeable dependent on inflammation and gut environment. We found consistent high expression of Ly6C, Cd62L, previously undescribed Trem1 and Ccr7 in Ly6Chigh macrophages and Cd206 and Cx3cr1 in Ly6Clow/neg cell population in different mice. However, signature genes showed that resident macrophages but not inflammatory macrophages were highly conserved in normal and inflamed mice. Gut microbiota play a role in accumulation and differentiation of gut macrophages. Both Ly6Chigh and Ly6Clow macrophages in intestine and colon tissues are similar. These uncover the transcriptional landscape and phenotypic heterogeneity of CD11b+ cells, especially macrophages in gut tissues.

2019-10-16 | GSE138902 | GEO

A gut commensal protist protects against virus-mediated loss of oral tolerance

Project description:To better understand how Tritrichomonas arnold colonization impacts the reovirus-mediated proinflammatory response in dietary antigen-presenting dendtric cells (cDC1), we examined the transcriptional profile of mesenteric lymph node-derived cDC1. For RNA-sequencing on CD103+ CD11b- CD8a+ DCs, 1,000 CD103+ CD11b- CD8a+ DCs were FACS sorted into a 96-well plate

2023-06-07 | GSE230530 | GEO

RNA-seq of BV2 cultured microglia following high glucose and CD200Fc treatments

Project description:We observe dyseregulated CD200-CD200R signaling in early diabetes that correlates with microglia-mediated neuroretinopathy and found that CD200 fusion protein (CD200Fc), an agonist of CD200R, attenuated high glucose-induced inflammation in cultured microglia. Therefore, we performed RNA-Sequencing on cultured BV2 microglia following exposure to normal or high glucose media (NG, HG) with or without CD200Fc supplementation (50ng/mL) to investigate broader biologic implications.

2023-10-30 | GSE238008 | GEO