Combined multivariate and pathway analyses show that Allergen-induced gene expression changes in CD4 + T cells are reversed by glucocorticoids

Abstract

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, P<0.0001). 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. © 2012 Zhao et al.