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Series GSE119257 Query DataSets for GSE119257
Status Public on Mar 19, 2019
Title The non-canonical Notch ligand DNER regulates IFNγ in macrophages during COPD progression
Organism Mus musculus
Experiment type Expression profiling by array
Summary Chronic Obstructive Pulmonary Diseases (COPD) is the third leading cause of death worldwide with no curative therapy available. A novel non-canonical Notch ligand, DNER, has been identified in a GWAS to correlate with disease severity, but its function and contribution to COPD is completely unknown. DNER localization and expression was determined in COPD patients and 6 month cigarette smoke (CS)-exposed mice. Microarray and GSEA of M1 and M2 bone marrow-derived macrophages (BMDM) from wild type (WT) and Dner deficient mice were performed. IFNγ levels and Notch activation were evaluated in 2 month CS-exposed WT and Dner deficient mice. Notch and NFκB pathways were evaluated by qPCR and Western Blot in BMDM. DNER was increased in the lung of COPD patients and localized to macrophages in human and murine lung tissue. Upon pro-inflammatory conditions, WT BMDM and human macrophages exhibited increased Dner levels. Interestingly, IFNγ responses were abrogated in Dner deficient pro-inflammatory macrophages both in vitro and in vivo. LPS treated Dner deficient BMDM failed to trigger NFκB and Notch signalling cascades evidenced by the absence of nuclear active forms. We provide the first molecular and functional insights into DNER, a novel Notch ligand that controls IFNγ secretion in lung recruited pro-inflammatory macrophages.
 
Overall design We performed gene expression microarray analysis of M0, M1 and M2 bone marrow-derived macrophages (BMDM) from wild type (WT) and Dner-deficient mice
 
Contributor(s) Ballester-López C, Conlon TM, Ertüz Z, Greiffo F, Irmler M, Beckers J, Fernandez IE, Eickelberg O, Yildirim AO
Citation(s) 31060902
Submission date Aug 30, 2018
Last update date Jun 18, 2019
Contact name Johannes Beckers
E-mail(s) beckers@helmholtz-muenchen.de
Organization name Helmholtz Zentrum Muenchen
Department Institute of Experimental Genetics
Street address Ingolstaedter Landstr. 1
City Neuherberg
ZIP/Postal code 85764
Country Germany
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (18)
GSM3362364 M0 BMDM of Dner-deficient mice_rep1
GSM3362365 M0 BMDM of Dner-deficient mice_rep2
GSM3362366 M0 BMDM of Dner-deficient mice_rep3
Relations
BioProject PRJNA488621

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE119257_RAW.tar 155.9 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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