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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
BMC Genomics. 2009; 10: 233.
Published online May 18, 2009. doi:  10.1186/1471-2164-10-233
PMCID: PMC2689280
Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells
K Emelie M Blomberg,corresponding author1 Nicole Boucheron,2 Jessica M Lindvall,3 Liang Yu,1 Julia Raberger,2 Anna Berglöf,1 Wilfried Ellmeier,2 and CI Edvard Smithcorresponding author1
1Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Huddinge, Sweden
2Division of Immunobiology, Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria
3Department for Informatics, Center for Bioinformatics, Post box 1080 Blindern NO-0316, Oslo, Norway
corresponding authorCorresponding author.
K Emelie M Blomberg: emelie.blomberg/at/; Nicole Boucheron: nicole.boucheron/at/; Jessica M Lindvall: jessli/at/; Liang Yu: liang.yu/at/; Julia Raberger: julia.raberger/at/; Anna Berglöf: anna.berglof/at/; Wilfried Ellmeier: Wilfried.Ellmeier/at/; CI Edvard Smith: edvard.smith/at/
Received November 6, 2008; Accepted May 18, 2009.
The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3+ T-cells, including CD4+ and CD8+ subsets, using Affymetrix microarrays.
The largest difference between Itk-/- and Wt CD3+ T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4+ and CD8+ T-cell subsets identified a greater differential expression than in total CD3+ cells. Cyclosporin A (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the Bub1, IL7R, Ctla2a, Ctla2b, and Schlafen1 genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found.
Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.
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