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Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4(+) T Cells Are Reversed by Glucocorticoids
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.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
University of Padua, Italy .
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 6Article in journal (Refereed) Published
Abstract [en]

Background: Glucocorticoids (GCs) play a key role in the treatment of allergy. However, the genome-wide effects of GCs on gene expression in allergen-challenged CD4(+) T cells have not been described. The aim of this study was to perform a genome-wide analysis to investigate whether allergen-induced gene expression changes in CD4(+) T cells could be reversed by GCs. Methodology/Principal Findings: Gene expression microarray analysis was performed to profile gene expression in diluent( D), allergen- (A), and allergen + hydrocortisone- (T) challenged CD4(+) T cells from patients with seasonal allergic rhinitis. Principal component analysis (PCA) showed good separation of the three groups. To identify the correlation between changes in gene expression in allergen-challenged CD4(+) T cells before and after GC treatment, we performed orthogonal partial least squares discriminant analysis (OPLS-DA) followed by Pearson correlation analysis. This revealed that allergen-induced genes were widely reversed by GC treatment (r = -0.77, Pless than0.0001). We extracted 547 genes reversed by GC treatment from OPLS-DA models based on their high contribution to the discrimination and found that those genes belonged to several different inflammatory pathways including TNFR2 Signalling, Interferon Signalling, Glucocorticoid Receptor Signalling and T Helper Cell Differentiation. The results were supported by gene expression microarray analyses of two independent materials. Conclusions/Significance: Allergen-induced gene expression changes in CD4(+) T cells were reversed by treatment with glucocorticoids. The top allergen-induced genes that reversed by GC treatment belonged to several inflammatory pathways and genes of known or potential relevance for allergy.

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Public Library of Science , 2012. Vol. 7, no 6
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-79798DOI: 10.1371/journal.pone.0039016ISI: 000305340000060OAI: oai:DiVA.org:liu-79798DiVA: diva2:544985
Available from: 2012-08-17 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved

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Wang, HuiGustafsson, MikaBruhn, SörenBenson, Mikael

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