NFAT公司
生物
CD3型
CD28
T细胞受体
T细胞
CD8型
染色质免疫沉淀
转录组
Jurkat细胞
ZAP70型
分子生物学
细胞生物学
免疫学
转录因子
基因表达
免疫系统
遗传学
基因
发起人
作者
K. Emelie M. Blomberg,Nicole Boucheron,Jessica M. Lindvall,Liang Yu,Julia Raberger,Anna Berglöf,Wilfried Ellmeier,C. I. Edvard Smith
出处
期刊:BMC Genomics
[Springer Nature]
日期:2009-01-01
卷期号:10 (1): 233-233
被引量:20
标识
DOI:10.1186/1471-2164-10-233
摘要
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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