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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3656-3664. Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-10-4190. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4190v1 107/9/3656    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 Fujita, S. Articles by Sato, K. Search for Related Content PubMed PubMed Citation Articles by Fujita, S. Articles by Sato, K. Related Collections Immunobiology Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Regulatory dendritic cells act as regulators of acute lethal systemic inflammatory response Shigeharu Fujita, Ken-ichiro Seino, Kaori Sato, Yumiko Sato, Kawori Eizumi, Naohide Yamashita, Masaru Taniguchi, and Katsuaki Sato From the Laboratory for Dendritic Cell Immunobiology and the Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan; the Department of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Bacterial infection triggers host inflammation through the activation of immune cells, leading to the elimination of bacteria. However, the regulatory mechanisms of the host inflammatory response remain unknown. Here we report that a subset of potent tolerogenic dendritic cells (DCs), regulatory DCs (DCregs), control the systemic inflammatory response. Unlike normal DCs, which produced proinflammatory cytokines in response to bacterial lipopolysaccharide (LPS), DCregs produced fewer proinflammatory cytokines and instead preferentially produced interleukin-10 (IL-10), and these events involved the expression of IBNS and Bcl-3 as well as cyclic AMP (cAMP)-mediated activation of protein kinase A (PKA). In addition, DCregs not only suppressed LPS-induced production of proinflammatory cytokines in macrophages, but also reduced their serum levels in mice. Furthermore, DCregs protected mice against the lethality induced by experimental endotoxemia and bacterial peritonitis. The inhibitory effect of DCregs against inflammatory responses involved the production of IL-10. On the other hand, naturally existing tolerogenic DC subsets producing IL-10, CD11clowCD45RBhigh DCs, also suppressed LPS-induced host inflammatory responses. Thus, a subset of tolerogenic DCs act as potential regulators of the host inflammatory response, and they might have preventive and therapeutic potential for the treatment of systemic as well as local inflammatory diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dendritic cells get VIP treatment Edmund K. Waller Blood 2006 107: 3423-3424. [Full Text] [PDF] This article has been cited by other articles: I D Iliev, I Spadoni, E Mileti, G Matteoli, A Sonzogni, G M Sampietro, D Foschi, F Caprioli, G Viale, and M Rescigno Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells Gut, November 1, 2009; 58(11): 1481 - 1489. [Abstract] [Full Text] [PDF] K. Sato, K. Eizumi, T. Fukaya, S. Fujita, Y. Sato, H. Takagi, M. 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[Full Text] [PDF] I. D. Jung, M.-G. Lee, J. H. Chang, J. S. Lee, Y.-I. Jeong, C.-M. Lee, W. S. Park, J. Han, S.-K. Seo, S. Y. Lee, et al. Blockade of Indoleamine 2,3-Dioxygenase Protects Mice against Lipopolysaccharide-Induced Endotoxin Shock J. Immunol., March 1, 2009; 182(5): 3146 - 3154. [Abstract] [Full Text] [PDF] M. Zhang, B. E. Berndt, J.-J. Chen, and J. Y. Kao Expression of a Soluble TGF-{beta} Receptor by Tumor Cells Enhances Dendritic Cell/Tumor Fusion Vaccine Efficacy J. Immunol., September 1, 2008; 181(5): 3690 - 3697. [Abstract] [Full Text] [PDF] E. L. Gautier, T. Huby, F. Saint-Charles, B. Ouzilleau, M. J. Chapman, and P. Lesnik Enhanced Dendritic Cell Survival Attenuates Lipopolysaccharide-Induced Immunosuppression and Increases Resistance to Lethal Endotoxic Shock J. Immunol., May 15, 2008; 180(10): 6941 - 6946. [Abstract] [Full Text] [PDF] K. N. Couper, D. G. Blount, and E. M. Riley IL-10: The Master Regulator of Immunity to Infection J. 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