Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells
dc.contributor.author | M Blomberg, K E | |
dc.contributor.author | Boucheron, Nicole | |
dc.contributor.author | Lindvall, Jessica M | |
dc.contributor.author | Yu, Liang | |
dc.contributor.author | Raberger, Julia | |
dc.contributor.author | Berglöf, Anna | |
dc.contributor.author | Ellmeier, Wilfried | |
dc.contributor.author | Smith, CI E | |
dc.date.accessioned | 2015-10-09T01:02:40Z | |
dc.date.available | 2015-10-09T01:02:40Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | BMC Genomics. 2009 May 18;10(1):233 | |
dc.identifier.uri | http://hdl.handle.net/10852/46294 | |
dc.description.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. | |
dc.language.iso | eng | |
dc.rights | Blomberg et al. | |
dc.rights | Attribution 2.0 Generic | |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0/ | |
dc.title | Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells | |
dc.type | Journal article | |
dc.date.updated | 2015-10-09T01:02:41Z | |
dc.creator.author | M Blomberg, K E | |
dc.creator.author | Boucheron, Nicole | |
dc.creator.author | Lindvall, Jessica M | |
dc.creator.author | Yu, Liang | |
dc.creator.author | Raberger, Julia | |
dc.creator.author | Berglöf, Anna | |
dc.creator.author | Ellmeier, Wilfried | |
dc.creator.author | Smith, CI E | |
dc.identifier.doi | http://dx.doi.org/10.1186/1471-2164-10-233 | |
dc.identifier.urn | URN:NBN:no-50549 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/46294/1/12864_2008_Article_2117.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 233 |
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