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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3457-3464. Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2004-12-4965. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-12-4965v1 106/10/3457    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by O'Keeffe, M. Articles by Gerondakis, S. Search for Related Content PubMed PubMed Citation Articles by O'Keeffe, M. Articles by Gerondakis, S. Related Collections Immunobiology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Distinct roles for the NF-B1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals Meredith O'Keeffe, Raelene J. Grumont, Hubertus Hochrein, Martina Fuchsberger, Raffi Gugasyan, David Vremec, Ken Shortman, and Steve Gerondakis From the The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and the Department of Medical Microbiology, Immunology and Hygiene, Technical Univeristy of Munich, Munich, Germany. Reticuloendotheliosis viral oncogene homolog/nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Rel/NF-B) activation is a ubiquitous outcome of engaging Toll-like receptors (TLRs), yet the cell-type–specific functions of this pathway in response to particular microbial signals remain poorly defined. Here we show that NF-B1 and C-Rel, Rel/NF-B proteins induced in conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) by cytosine-phosphate-guanosine (CpG) DNA, a TLR-9 ligand, serve markedly different functions in these DC subsets. With the exception of impaired interleukin-12 (IL-12) production, cultured Nfkb1–/–C-Rel–/– cDCs responded relatively normally to CpG DNA. In contrast, CpG-treated Nfkb1–/–C-Rel–/– pDCs, which were still able to produce type I interferon and regulated on activation normal T-cell expressed and secreted (RANTES), but not IL-6 or IL-12, failed to acquire an activated dendritic phenotype and underwent apoptosis. Although the TLR-9–mediated death of Nfkb1–/–C-Rel–/– pDCs, which coincided with a failure to up-regulate the prosurvival proteins B-cell lymphoma apoptosis regulator xL (Bcl-xL) and A1, was blocked by Bcl-2 transgene expression, this inhibition of apoptosis still failed to rescue the differentiation defects. This indicated that these NF-B transcription factors independently regulate TLR-9–mediated pDC morphogenesis and survival. Collectively, these findings establish that NF-B1 and c-Rel, while largely dispensable for TLR-9–induced cDC activation, are critical for regulating differentiation and survival programs during pDC activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. F. Lind, C. L. Ahonen, A. Wasiuk, Y. Kosaka, B. Becher, K. A. Bennett, and R. J. Noelle Dendritic Cells Require the NF-{kappa}B2 Pathway for Cross-Presentation of Soluble Antigens J. Immunol., July 1, 2008; 181(1): 354 - 363. [Abstract] [Full Text] [PDF] A. Iparraguirre, J. W. Tobias, S. E. Hensley, K. S. Masek, L. L. Cavanagh, M. Rendl, C. A. Hunter, H. C. Ertl, Ulrich. H. von Andrian, and W. Weninger Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide J. Leukoc. Biol., March 1, 2008; 83(3): 610 - 620. [Abstract] [Full Text] [PDF] C. Guiducci, C. Ghirelli, M.-A. Marloie-Provost, T. Matray, R. L. Coffman, Y.-J. Liu, F. J. Barrat, and V. Soumelis PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation J. Exp. Med., February 18, 2008; 205(2): 315 - 322. [Abstract] [Full Text] [PDF] X. Wang, S. Hussain, E.-J. Wang, X. Wang, M. O. Li, A. Garcia-Sastre, and A. A. Beg Lack of Essential Role of NF-{kappa}B p50, RelA, and cRel Subunits in Virus-Induced Type 1 IFN Expression J. Immunol., June 1, 2007; 178(11): 6770 - 6776. [Abstract] [Full Text] [PDF] J. Wang, X. Wang, S. Hussain, Y. Zheng, S. Sanjabi, F. Ouaaz, and A. A. Beg Distinct Roles of Different NF-{kappa}B Subunits in Regulating Inflammatory and T Cell Stimulatory Gene Expression in Dendritic Cells J. Immunol., June 1, 2007; 178(11): 6777 - 6788. [Abstract] [Full Text] [PDF] L. Chen, M. Arora, M. Yarlagadda, T. B. Oriss, N. Krishnamoorthy, A. Ray, and P. Ray Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide J. Immunol., August 15, 2006; 177(4): 2373 - 2383. [Abstract] [Full Text] [PDF]

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