Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance
| العنوان: | Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance |
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| المؤلفون: | Brian T. Abe, Fernando Macian, Noemi Soto-Nieves, Anjana Rao, Ian Baine, Irene Puga, Sanmay Bandyopadhyay |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Transcription, Genetic, T-Lymphocytes, Ubiquitin-Protein Ligases, T cell, Immunology, Receptors, Antigen, T-Cell, Biology, Jurkat cells, Article, Immune tolerance, Jurkat Cells, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Immune Tolerance, medicine, Humans, Immunology and Allergy, Promoter Regions, Genetic, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, NFATC Transcription Factors, Caspase 3, T-cell receptor, NFAT, Cell Biology, Molecular biology, medicine.anatomical_structure, Gene Expression Regulation, Mutation, Dimerization, 030215 immunology |
| الوصف: | In T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6074cbc81182b09bda003cdc3f7c3214Test https://doi.org/10.1084/jem.20082731Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6074cbc81182b09bda003cdc3f7c3214 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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