Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells

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Abstract

Background: 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. Results: 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. Conclusion: Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk. © 2009 Blomberg et al; licensee BioMed Central Ltd.

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Blomberg, K. E. M., Boucheron, N., Lindvall, J. M., Yu, L., Raberger, J., Berglöf, A., … Smith, C. I. E. (2009). Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells. BMC Genomics, 10. https://doi.org/10.1186/1471-2164-10-233

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