Combining gene expression microarray- and cluster analysis with sequence-based predictions to identify regulators of IL-13 in allergy

Bruhn, Sören,1976-Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Center for individualized medication (author)

funding agencies|European Commission|223367|Swedish Medical Research Council||
The Th2 cytokine IL-13 plays a key role in allergy, by regulating IgE, airway hyper secretion, eosinophils and mast cells. In this study, we aimed to identify novel transcription factors (TFs) that potentially regulated IL-13. We analyzed Th2 polarized naïve T cells from four different blood donors with gene expression microarrays to find clusters of genes that were correlated or anti-correlated with IL13. These clusters were further filtered, by selecting genes that were functionally related. In these clusters, we identified three transcription factors (TFs) that were predicted to regulate the expression of IL13, namely CEBPB, E2F6 and AHR. siRNA mediated knockdowns of these TFs in naïve polarized T cells showed significant increases of IL13, following knockdown of CEBPB and E2F6, but not AHR. This suggested an inhibitory role of CEBPB and E2F6 in the regulation of IL13 and allergy. This was supported by analysis of E2F6, but not CEBPB, in allergen-challenged CD4+ T cells from six allergic patients and six healthy controls, which showed decreased expression of E2F6 in patients. In summary, our findings indicate an inhibitory role of E2F6 in the regulation of IL-13 and allergy. The analytical approach may be generally applicable to elucidate the complex regulatory patterns in Th2 cell polarization and allergy.

Katzenellenbogen, MarkLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Center for individualized medication (author)
Gustafsson, Mika,1977-Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Center for individualized medication(Swepub:liu)mikgu75 (author)
Krönke, AndreaCenix BioScience GmbH, Dresden, Germany (author)
Sönnichsen, BirteCenix BioScience GmbH, Dresden, Germany (author)
Zhang, HuanLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Center for individualized medication(Swepub:liu)huazh47 (author)
Benson, MikaelLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Center for individualized medication(Swepub:liu)mikbe05 (author)
Linköpings universitetInstitutionen för klinisk och experimentell medicin (creator_code:org_t)

By the author/editor: Bruhn, Sören, 19 ...; Katzenellenbogen ...; Gustafsson, Mika ...; Krönke, Andrea; Sönnichsen, Birt ...; Zhang, Huan; show more...; Benson, Mikael; show less...

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