Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells
| Autor: | Liang Yu, Jessica M. Lindvall, Nicole Boucheron, Julia Raberger, K. Emelie M. Blomberg, Wilfried Ellmeier, Anna Berglöf, C. I. Edvard Smith |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
lcsh:QH426-470 CD3 Complex Transcription Genetic CD3 lcsh:Biotechnology CD8-Positive T-Lymphocytes Proteomics Lymphocyte Activation Transcriptome Mice CD28 Antigens T-Lymphocyte Subsets lcsh:TP248.13-248.65 Genetics Cytotoxic T cell Animals Oligonucleotide Array Sequence Analysis Mice Knockout biology NFATC Transcription Factors Kinase Gene Expression Profiling Protein-Tyrosine Kinases Molecular biology Gene expression profiling Mice Inbred C57BL lcsh:Genetics biology.protein Cyclosporine DNA microarray CD8 Biotechnology Research Article |
| Zdroj: | BMC Genomics BMC Genomics, Vol 10, Iss 1, p 233 (2009) |
| ISSN: | 1471-2164 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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