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  • Zhao, YelinLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet (author)

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

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-06-12
  • Public Library of Science,2012
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:liu-79798
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-79798URI
  • https://doi.org/10.1371/journal.pone.0039016DOI
  • https://gup.ub.gu.se/publication/160363URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • 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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  • Wang, HuiGothenburg University,Göteborgs universitet,Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xwanhu (author)
  • Gustafsson, MikaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet(Swepub:liu)mikgu75 (author)
  • Muraro, AntonellaUniversity of Padua, Italy (author)
  • Bruhn, SörenLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet(Swepub:liu)sorbr27 (author)
  • Benson, MikaelLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet(Swepub:gu)xbenmi (author)
  • Linköpings universitetInstitutionen för klinisk och experimentell medicin (creator_code:org_t)

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  • In:PLOS ONE: Public Library of Science7:61932-6203

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