title: Genome-wide transcriptional analysis of T cell activation reveals differential gene expression associated with psoriasis.
abstract: BACKGROUND
  Psoriasis is a chronic autoimmune disease in which T cells have a predominant role in initiating and perpetuating the chronic inflammation in skin. However, the mechanisms that regulate T cell activation in psoriasis are still incompletely understood. The objective of the present study was to characterize the main genetic pathways associated with T cell activation in psoriasis.
  
  
  RESULTS
  Gene expression profiles from in vitro activated T cells were obtained from 17 psoriasis patients and 7 healthy controls using Illumina HT-12 v4 microarrays. From a total of 47,321 analyzed transcripts, 42 genes were found to be differentially expressed between psoriasis and controls (FDR p-value < 0.1, absolute fold-change > 1.2). Using an independent cohort of 8 patients and 8 healthy controls we validated the overexpression of SPATS2L (p-value =0.0009) and KLF6 (p-value =0.0012) genes in activated T cells from psoriasis patients. Using weighted correlation analysis we identified SPATS2L and KLF6 coexpression networks, which were also significantly associated with psoriasis (p-value < 0.05). Gene Ontology analysis allowed the identification of several biological processes associated with each coexpression network. Finally, using Gene Set Enrichment Analysis over the global T cell transcriptome we also found additional genetic pathways strongly associated with psoriasis (p-value < 0.0001).
  
  
  CONCLUSIONS
  This study has identified two new genes, SPATS2L and KLF6, strongly associated with T cell activation in psoriasis. Functional analyses of the gene expression profiles also revealed new biological processes and genetic pathways associated with psoriasis. The results of this study provide an important insight into the biology of this common chronic inflammatory disease.
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona 08035, Spain. sara.marsal@vhir.org.
authors.forename: Nuria
authors.initials: N
authors.lastname: Palau
authors.forename: Antonio
authors.initials: A
authors.lastname: Julià
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrándiz
authors.forename: Lluís
authors.initials: L
authors.lastname: Puig
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fonseca
authors.forename: Emilia
authors.initials: E
authors.lastname: Fernández
authors.forename: María
authors.initials: M
authors.lastname: López-Lasanta
authors.forename: Raül
authors.initials: R
authors.lastname: Tortosa
authors.forename: Sara
authors.initials: S
authors.lastname: Marsal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology*