Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
PLoS One. 2012;7(6):e39016. doi: 10.1371/journal.pone.0039016. Epub 2012 Jun 12.
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.
糖皮质激素（GCs）在过敏治疗中起着关键作用。然而，GC 对变应原刺激的 CD4+T 细胞基因表达的全基因组效应尚未描述。本研究旨在进行全基因组分析，以研究 GC 是否可以逆转 CD4+T 细胞中变应原诱导的基因表达变化。
方法/主要发现：对季节性变应性鼻炎患者的稀释剂（D）、变应原（A）和变应原+氢化可的松（T）刺激的 CD4+T 细胞进行基因表达微阵列分析，以描绘基因表达谱。主成分分析（PCA）显示三组之间有良好的分离。为了确定 GC 治疗前后变应原刺激的 CD4+T 细胞基因表达变化之间的相关性，我们进行了正交偏最小二乘判别分析（OPLS-DA），然后进行 Pearson 相关分析。这表明 GC 治疗广泛逆转了变应原诱导的基因（r=−0.77，P<0.0001）。我们从 OPLS-DA 模型中提取了 547 个 GC 治疗逆转的基因，基于它们对判别分析的高贡献，发现这些基因属于几个不同的炎症途径，包括 TNFR2 信号、干扰素信号、糖皮质激素受体信号和 T 辅助细胞分化。两个独立材料的基因表达微阵列分析结果支持了这一结果。
结论/意义：GC 治疗逆转了 CD4+T 细胞中变应原诱导的基因表达变化。GC 治疗逆转的顶级变应原诱导基因属于几个炎症途径和已知或潜在与过敏相关的基因。
