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


RESULTS
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
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.
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Yelin
Y
Zhao
Hui
H
Wang
Mika
M
Gustafsson
Antonella
A
Muraro
Sören
S
Bruhn
Mikael
M
Benson
D000328:Adult; D000485:Allergens / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone; D007558:Italy; D008297:Male; D046228:Microarray Analysis; D025341:Principal Component Analysis; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D013548:Sweden
D000485:Allergens; D005938:Glucocorticoids; D006854:Hydrocortisone