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Open Access Highly Accessed Research article

Genome-wide transcriptional analysis of T cell activation reveals differential gene expression associated with psoriasis

Nuria Palau1, Antonio Julià1, Carlos Ferrándiz2, Lluís Puig3, Eduardo Fonseca4, Emilia Fernández5, María López-Lasanta1, Raül Tortosa1 and Sara Marsal1*

Author Affiliations

1 Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona 08035, Spain

2 Dermatology Service, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain

3 Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona 08040, Spain

4 Dermatology Service, Hospital Abente y Lago, La Coruña 15001, Spain

5 Dermatology Service, Hospital Universitario de Salamanca, Salamanca 37007, Spain

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BMC Genomics 2013, 14:825  doi:10.1186/1471-2164-14-825

Published: 23 November 2013

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.

Keywords:
Psoriasis; T cell; Gene expression; Microarray; Genetic pathway; Gene network