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| Status |
Public on Jul 08, 2015 |
| Title |
IL-10 production and metabolic regulation in macrophages are linked by a TLR-driven CREB-mediated mechanism |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections macrophages are an important source of IL-10, however the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. Here, bone marrow derived macrophages exposed to Excretory/Secretory (E/S) products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK/ERK/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Uptake of cercarial E/S products by phagocytosis was critical for the production of IL-10 and the activation of MAPKs and CREB, which indicates that interactions between E/S products with TLR2 and TLR4, may be occurring in endosomes. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. Moreover, skin resident tissue macrophages, which encounter S. mansoni E/S products during infection, are the first monocytes to produce IL-10 in vivo early after infection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site. To conclude, we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state.
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| Overall design |
CREB binding sites 3 pooled samples of stimulated bone marrow macrophages
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| Contributor(s) |
Sanin DE, Prendergast CT, Mountford AP |
| Citation(s) |
26116503 |
| Submission date |
Jan 09, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
David E Sanin |
| E-mail(s) |
sanin@ie-freiburg.mpg.de
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| Organization name |
Max-Planck-Institute für Immunbiologie und Epigenetik
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| Department |
Immunometabolism
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| Lab |
Pearce
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| Street address |
Stübeweg 51
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| City |
Freiburg im Breisgau |
| ZIP/Postal code |
79108 |
| Country |
Germany |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA272149 |
| SRA |
SRP051981 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE64844_CREB_annotated_peaks.txt.gz |
92.5 Kb |
(ftp)(http) |
TXT |
| GSE64844_CREB_peaks.stats.txt.gz |
916 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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