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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Crohn's disease risk variant in GPR65 alters lysosomal function

ABSTRACT: Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function. Bone marrow-derived macrophages from WT or Gpr65-/- mice were harvested for RNA analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Ramnik Xavier

PROVIDER: E-GEOD-69445 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk.

Lassen Kara G KG McKenzie Craig I CI Mari Muriel M Murano Tatsuro T Begun Jakob J Baxt Leigh A LA Goel Gautam G Villablanca Eduardo J EJ Kuo Szu-Yu SY Huang Hailiang H Macia Laurence L Bhan Atul K AK Batten Marcel M Daly Mark J MJ Reggiori Fulvio F Mackay Charles R CR Xavier Ramnik J RJ

Immunity 20160607 6

Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function. Mice lacking Gpr65, a proton-sensing G protein-coupled receptor, showed increased susceptibly to bacteria-induced colitis. Epithelial cells and macro ...[more]

PMID: 27287411

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Crohn's disease risk variant in GPR65 alters lysosomal function

Project description:Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function.

2016-06-15 | GSE69445 | GEO

Pharmacological inhibition of 17β-hydroxysteroid dehydrogenase inhibits endometrial cancer growth in an orthotopic xenograft mouse model

Project description:Experimental design: Endometrial tumours were induced orthotopically (in one uterine horn) in 8-week-old female athymic nude mice (Crl:NU(NCr)-Foxn1nu), using an Ishikawa-derived cell line (clones Ishi-M3-HSDA, described in Konings et al 2018). This cell line maintains the characteristics of the parental line (i.e., gives rise to well differentiated-estrogen sensitive adenocarcinomas) and further bears the luciferase gene for in vivo measurement of tumour growth by bioluminescence and expresses the enzyme 17β-hydroxysteroid dehydrogenase (HSD17B1). After tumour engraftment (approximately two weeks), baseline was defined, mice were ovariectomised (to remove the natural source of estrogens) and estrone was supplemented via subcutaneous pellets at a dose of 0.02 g/day. Mice were further assigned to one arm, receiving only estrone, and a second arm, receiving estrone plus the HSD17B1 inhibitor FP4643 at a dose of 25mg/Kg. At humane endpoint (approximately 10 weeks), mice were sacrificed, primary tumours were excised and snap-frozen. Tumours were divided on their largest diameter plane and slices for RNA isolation were prepared from such largest surface area of the primary tumours. Histology on mirror slices confirmed the present of tumour tissue and the absence of necrosis, inflammation and mouse endometrium.

2021-04-09 | E-MTAB-10338 | biostudies-arrayexpress

Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages.

Project description:Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P(1)-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-122]

2012-01-27 | E-BUGS-122 | biostudies-arrayexpress

TUBE pulldown of K63 ubiquitylated proteins from phagosomes

Project description:TUBE TAB2 pull down of K63 polyubiquitylated proteins from phagosomes isolated from mouse macrophages.

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2023-01-18 | PXD033010 | Pride

Candida albicans phagocytosed by macrophages: intact vs. ruptured phagosomes

Project description:Candida albicans phagocytosed by macrophages: intact vs. ruptured phagosomes

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Ribosomal protein RPL20B modulates cytokine production by macrophage in reponse to yeast

Project description:Phagocytosis is the process by which myeloid phagocytes bind and internalize potentially dangerous microbes. During phagocytosis, innate immune receptors and the associated signaling adapters are localized to the maturing phagosome compartment. We used proximity labeling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria and identified programmed death-ligand 1 (PD-L1) as a protein that specifically enriches in phagosomes containing yeast. We found that PD-L1 directly binds to yeast upon processing in phagosomes. By surface display library screening, we identified the ribosomal protein RPL20B as a fungal protein ligand for PD-L1. Using an auxin-inducible depletion system, we found that detection of RPL20B by macrophages influences production of a subset of inflammatory cytokines and chemokines produced when macrophages encounter yeast.

2024-04-19 | GSE235078 | GEO

Comparative transcriptomics of B cell transdifferentiation in human and mouse. ChIP-Seq data

Project description:Exogenous overexpression of CEBPA transcription factor induces transdifferentiation from pro B cells into functional macrophages. Here we report the CEBPA binding ChIP-Seq data at 12 hours time point after induction of transdifferentiation in human BLaER1 cells (Rapino et al. 2013).

2022-01-01 | E-MTAB-7114 | biostudies-arrayexpress

Temporal and ligand effects on phagosome maturation

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