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Series GSE60083 Query DataSets for GSE60083
Status Public on Aug 06, 2014
Title Genome-wide analysis of monocyte derived macrophages from Crohn's Disease patients and controls
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory disorder, primarily affecting the gastrointestinal tract. Genetic and functional studies have highlighted a key role for innate immunity in its pathogenesis. Profound systemic defects in innate immunity and acute inflammation are understood to result in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes. Macrophages, key orchestrators of acute inflammation, are likely to play an important role in the initial impaired innate immune response. Monocyte-derived macrophages from CD patients stimulated with E. coli were shown to release attenuated levels of TNF and IFNγ with normal secretion of IL8, IL10 and IL6. In controls, the secretion of these cytokines was strongly positively correlated, which was not seen with CD macrophages. The transcriptomes of CD and control macrophages were examined in an attempt to understand the molecular basis of this defect. There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients. The most common of these was optineurin (OPTN) which was under-expressed in approximately 10% of the CD patients. Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with siRNA knockdown in THP-1 cells. Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.
 
Overall design Total RNA obtained from monocyte derived macrophages from Crohn's disease patients (n=58) or healthy volenteers (n=42) were cultured for six days before being stimulated with heat killed E. coli for four hours or left unstimulated.
 
Contributor(s) Smith AM, Sewell GW, Levine AP, Segal AW
Citation(s) 24943399
Submission date Aug 04, 2014
Last update date Feb 18, 2019
Contact name Tony Segal
E-mail(s) t.segal@ucl.ac.uk
Organization name UCL
Department Medicine
Street address 5 University Street
City London
ZIP/Postal code WC1E 6JJ
Country United Kingdom
 
Platforms (1)
GPL6884 Illumina HumanWG-6 v3.0 expression beadchip
Samples (100)
GSM1464665 HC139 Monocyte derived macrophage_Unstimulated
GSM1464666 HC158 Monocyte derived macrophage_Unstimulated
GSM1464667 CD232 Monocyte derived macrophage_Unstimulated
Relations
BioProject PRJNA257514

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60083_RAW.tar 6.3 Mb (http)(custom) TAR
GSE60083_non-normalized.txt.gz 23.2 Mb (ftp)(http) TXT
Processed data included within Sample table
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