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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 24, 2005 Accepted January 3, 2006 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* Laboratory for Dendritic Cell Immunobiology, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan; Department of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan Laboratory for Dendritic Cell Immunobiology, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan Department of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan * Corresponding author; email: katsuaki{at}rcai.riken.jp. 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 (DCreg), control the systemic inflammatory response. Unlike normal DCs, which produced proinflammatory cytokines in response to bacterial lipopolysaccharide (LPS), DCreg produced less proinflammatory cytokines and instead preferentially produced 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, DCreg not only suppressed LPS-induced production of proinflammatory cytokines in macrophages, but also reduced their serum levels in mice. Furthermore, DCreg protected mice against the lethality induced by experimental endotoxemia and bacterial peritonitis. The inhibitory effect of DCreg against inflammatory responses involved the production of IL-10. On the other hand, naturally existing tolerogenic DC subsets producing IL-10, CD11clowCD45RBhighDCs, 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. 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