Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids

BackgroundGlucocorticoids (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 FindingsGene 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, PTNFR2 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/SignificanceAllergen-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.