title: T-cell activation triggers death receptor-6 expression in a NF-κB and NF-AT dependent manner.
abstract: Death receptor-6 (DR6) apparently participates in the regulation of T-cell activation and/or activity as its genetic disruption results in enhanced CD4+ T-cell expansion, the production of Th2 cytokines, and interestingly also the compromised migration of CD4+ T cells to sites of inflammation. However, the mechanism of regulation of DR6 expression in cells of the immune system is not fully understood. In this communication we show that DR6 is not expressed in resting T cells from human peripheral blood or murine lymph nodes but that its expression is significantly upregulated in CD3 crosslinking- or PMA/ionomycin-activated T lymphocytes. DR6 expression is transiently increased in both activated human CD4+ and CD8+ T cells and it is apparently dependent on the activation of NF-κB and NF-AT signaling pathways. In contrast to primary peripheral blood T cells, the widely used model lymphoblastic leukemia T-cell line Jurkat is DR6-positive and unexpectedly, TCR-mediated stimulation of Jurkat cells strongly downregulates DR6 expression via suppression of its transcription.
authors.affiliation: Laboratory of Cell Signaling and Apoptosis, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220 Prague 4, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Klíma
authors.forename: Adéla
authors.initials: A
authors.lastname: Broučková
authors.forename: Michal
authors.initials: M
authors.lastname: Koc
authors.forename: Ladislav
authors.initials: L
authors.lastname: Anděra
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D017252:CD3 Complex; D007378:Interleukins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; C485251:Tnfrsf21 protein, mouse