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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3050-3061. Prepublished online as a Blood First Edition Paper on January 7, 2008; DOI 10.1182/blood-2007-11-122408. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-122408v1 111/6/3050    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 Escors, D. Articles by Collins, M. K. Search for Related Content PubMed PubMed Citation Articles by Escors, D. Articles by Collins, M. K. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Targeting dendritic cell signaling to regulate the response to immunization David Escors1, Luciene Lopes1, Rongtuan Lin2, John Hiscott2, Shizuo Akira3, Roger J. Davis4, and Mary K. Collins1 1 Infection and Immunity, University College London, London, United Kingdom; 2 Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC; 3 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and 4 Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester Dendritic cells (DCs) are key regulators of the immune system; they capture antigens and then can either stimulate an immune response or induce tolerance. Our aim was to activate individual DC signaling pathways to regulate the immune response. We therefore expressed constitutive activators of mitogen-activated protein kinase (MAPK) pathways or the interferon pathway, together with tumor antigens, using lentivectors. Triggering of p38 activated DCs substantially enhanced the antitumor immune response and prolonged survival of tumor-bearing mice. Activation of extracellular signal–regulated kinase (ERK) increased TGF-β expression while expression of a constitutively activated interferon regulatory factor-3 (IRF3) stimulated IL-10 secretion by DCs. ERK and IRF3 suppressed the immune response and stimulated expansion of regulatory T cells. These results provide a toolkit to regulate immune responses to viral vector or DC immunization; vaccine responses to foreign or tumor antigens can be enhanced and harmful responses to self-antigens or introduced transgenes can be reduced. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Zhao, C. Falk, W. Osen, M. Kato, D. Schadendorf, and V. Umansky Activation of p38 Mitogen-Activated Protein Kinase Drives Dendritic Cells to Become Tolerogenic in Ret Transgenic Mice Spontaneously Developing Melanoma Clin. Cancer Res., July 1, 2009; 15(13): 4382 - 4390. [Abstract] [Full Text] [PDF] K. Karwacz, S. Mukherjee, L. Apolonia, M. P. Blundell, G. Bouma, D. Escors, M. K. Collins, and A. J. Thrasher Nonintegrating Lentivector Vaccines Stimulate Prolonged T-Cell and Antibody Responses and Are Effective in Tumor Therapy J. Virol., April 1, 2009; 83(7): 3094 - 3103. [Abstract] [Full Text] [PDF] H. M. Rowe, L. Lopes, N. Brown, S. Efklidou, T. Smallie, S. Karrar, P. M. Kaye, and M. K. Collins Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-{kappa}B, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses J. Virol., February 15, 2009; 83(4): 1555 - 1562. [Abstract] [Full Text] [PDF]

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