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Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Östergötlands Läns Landsting.
Sahlgrenska University Hospital.
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2012 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 67, no 1, 33-40 p.Article in journal (Refereed) Published
Abstract [en]

Background: The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy. Methods: IRF4 and its target genes were examined in allergen-challenged CD4+ cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP-chips), computational target prediction, and RNAi knockdowns. Results: IRF4 increased in allergen-challenged CD4+ cells from patients with IAR, and functional studies supported its role in Th2 cell activation. IRF4 ChIP-chip showed that IRF4 regulated a large number of genes relevant to Th cell differentiation. However, neither Th1 nor Th2 cytokines were the direct targets of IRF4. To examine whether IRF4 induced Th2 cytokines via one or more downstream TFs, we combined gene expression microarrays, ChIP-chips, and computational target prediction and found a putative intermediary TF, namely ETS1 in allergen-challenged CD4+ cells from allergic patients. ETS1 increased significantly in allergen-challenged CD4+ cells from patients compared to controls. Gene expression microarrays before and after ETS1 RNAi knockdown showed that ETS1 induced Th2 cytokines as well as disease-related pathways. Conclusions: Increased expression of IRF4 in allergen-challenged CD4+ cells from patients with intermittent allergic rhinitis leads to activation of a complex transcriptional program, including Th2 cytokines.

Place, publisher, year, edition, pages
John Wiley and Sons , 2012. Vol. 67, no 1, 33-40 p.
Keyword [en]
Allergy, transcription factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-75112DOI: 10.1111/j.1398-9995.2011.02707.xISI: 000297921100007OAI: oai:DiVA.org:liu-75112DiVA: diva2:504547
Note
Funding Agencies|European Commission|223367|MultiMod||Swedish Medical Research Council||US National Institutes of Health|P01-DA-015027-01R01-MH-074460-01U01-AA-013512U01-AA-013641-04|US Department of Energy under the EPSCoR Laboratory||Available from: 2012-02-21 Created: 2012-02-17 Last updated: 2017-12-07

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Bruhn, SörenBarrenäs, FredrikWang, HuiBenson, Mikael

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Department of Clinical and Experimental MedicineFaculty of Health SciencesÖstergötlands Läns LandstingPediatrics
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Allergy. European Journal of Allergy and Clinical Immunology
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