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| Status |
Public on Jul 25, 2018 |
| Title |
Activation of IL5R and CRTH2 on Human Eosinophils Elicit a Similar Molecular Response and Reveal a Synergistic Effect |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Eosinophils represent key cells driving inflammatory processes in asthma and eosinophilic esophagitis (EoE). Eosinophils migration and activation in disease is orchestrated by a myriad of molecules among which prostaglandin D2, the cognate ligand of CRTH2, and interleukin 5 play a crucial role. In clinical studies with CRTH2 antagonists and anti-IL-5 antibodies, a reduction of the number of eosinophils in disease tissue of asthma and EoE patients was demonstrated, validating the pharmacological effects on eosinophils migration. In contrast, activation of eosinophils through IL5 or CRTH2 receptor has not been studied to the same extent. Understanding the molecular CRTH2 and IL5 activation bias in disease would provide a better assessment of pharmacological intervention, or the need for a combination therapy, to block eosinophils efficiently.
We performed gene expression profiling studies with isolated human eosinophils to compare the molecular signatures of CRTH2 and IL5 receptor activation. Furthermore we employed gene set enrichment analysis to query the eosinophils activation bias in asthma and EoE. We observed that activation of CRTH2 and IL5 on human eosinophils shared a large part of the molecular response but also present distinct molecular signatures. Remarkably, FADS1, involved in the synthesis of prostaglandin D2, was identified as a specific CRTH2-induced gene that is counter-regulated by IL5, potentially representing a feedback loop between CRTH2 and IL5 receptor.
In silico use of the identified gene signatures and FADS1 demonstrated an enrichment of the IL5 activation signature in lung tissue of asthma patients, whereas esophagus tissue of EoE patients presented a CRTH2 bias.
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| Overall design |
Comparison of IL-5 or dk-PGD2 stimulated human eosinophils against vehicle with 6 biological replicates for each condition.
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| Contributor(s) |
Murat A, Sippel V, Renault B, Hoerner J, Groenen PM, Strasser DS |
| Citation |
Sippel, V., Pierlot, G.M., Renault, B., Groenen, P.M.A. and Strasser, D.S., 2018. Activation of IL5R and CRTH2 on Human Eosinophils Elicit a Similar Molecular Response and Reveal a Synergistic Effect. European Journal of Molecular & Clinical Medicine, 5(1), pp.1 11. DOI: http://0-doi-org.brum.beds.ac.uk/10.5334/ejmcm.1
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| Submission date |
Nov 18, 2015 |
| Last update date |
Oct 25, 2018 |
| Contact name |
Axel Klenk |
| E-mail(s) |
axel.klenk@idorsia.com
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| Organization name |
Idorsia Pharmaceuticals Ltd.
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| Department |
Research Informatics
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| Street address |
Hegenheimermattweg 91
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| City |
Allschwil |
| ZIP/Postal code |
4123 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA302634 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75142_RAW.tar |
388.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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