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Series GSE145369 Query DataSets for GSE145369
Status Public on Jul 16, 2021
Title Serum mannose receptor promotes pro-inflammatory macrophage activation and obesity-associated metaflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Elevated serum concentrations of the soluble mannose receptor (sMR) have been reported to correlate with the severity of various inflammatory diseases. A physiological role of sMR, however, remains unclear. Here, we show that sMR binds CD45 on macrophages, both in vitro and in vivo, leading to cellular reprogramming towards an inflammatory phenotype by inhibition of CD45 phosphatase activity, which induces Src/Akt/NF-κB-mediated signaling. Remarkably, increased serum sMR levels correlate with obesity in both mice and humans. In addition, MR deficiency lowers the high-fat diet-induced increase in pro-inflammatory macrophages in metabolic tissues and protects against hepatic steatosis and whole-body metabolic dysfunctions. Conversely, administration of sMR induces serum pro-inflammatory cytokines and pro-inflammatory macrophages in the liver and promote insulin resistance. Altogether, our results reveal sMR as novel regulator of pro-inflammatory macrophage activation and could constitute a novel therapeutic target for hyperinflammatory diseases.
 
Overall design To dissect the effect of the soluble Mannose Receptor (MR) on macrophages, we treated MR-deficient macrophages with a recombinant fusion protein between the Fc region of human IgG1 and the extracellular region of the MR (FcMR) for 4 h, 12 h or 24 h and isolated mRNA for RNA-seq analysis.
 
Contributor(s) Schulte-Schrepping J, Embgenbroich M, Händler K, Schultze JL, Burgdorf S
Citation(s) 34326259
Submission date Feb 16, 2020
Last update date Oct 21, 2021
Contact name Joachim Schultze
E-mail(s) j.schultze@uni-bonn.de
Organization name LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
Department Genomics and Immunoregulation
Street address Carl-Troll-Strasse 31
City Bonn
State/province NRW
ZIP/Postal code 53115
Country Germany
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (21)
GSM4317388 3347_construct_untreated_0h_rep1
GSM4317389 3348_construct_untreated_0h_rep2
GSM4317390 3349_construct_untreated_0h_rep3
Relations
BioProject PRJNA606969
SRA SRP249656

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE145369_normalized_expression.csv.gz 2.9 Mb (ftp)(http) CSV
GSE145369_raw_expression.csv.gz 676.2 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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