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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1518-1527. Prepublished online as a Blood First Edition Paper on June 15, 2009; DOI 10.1182/blood-2008-12-192344. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-12-192344v1 114/8/1518    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 CrossRef Google Scholar Articles by Yoshizaki, M. Articles by Toyama-Sorimachi, N. PubMed PubMed Citation Articles by Yoshizaki, M. Articles by Toyama-Sorimachi, N. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q Mariko Yoshizaki1,*, Aya Tazawa1,*, Eiji Kasumi1,*, Shigemi Sasawatari1, Kenji Itoh2, Taeko Dohi1, Takehiko Sasazuki3, Kayo Inaba4, Andrew P. Makrigiannis5, and Noriko Toyama-Sorimachi1 1 Department of Gastroenterology, Research Institute, International Medical Center of Japan, Tokyo, Japan; 2 Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, University of Tokyo, Tokyo, Japan; 3 International Medical Center of Japan, Tokyo, Japan; 4 Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University and Japan Science and Technology Agency Core Research for Engineering, Science, and Technology, Kyoto, Japan; and 5 Laboratory of Molecular Immunology, Institute de Recherches Cliniques de Montreal, Montreal, QC Toll-like receptor (TLR) 9 recognizes unmethylated microorganismal cytosine guanine dinucleotide (CpG) DNA and elicits innate immune responses. However, the regulatory mechanisms of the TLR signaling remain elusive. We recently reported that Ly49Q, an immunoreceptor tyrosine-based inhibitory motif–bearing inhibitory receptor belonging to the natural killer receptor family, is crucial for TLR9-mediated type I interferon production by plasmacytoid dendritic cells. Ly49Q is expressed in plasmacytoid dendritic cells, macrophages, and neutrophils, but not natural killer cells. In this study, we showed that Ly49Q regulates TLR9 signaling by affecting endosome/lysosome behavior. Ly49Q colocalized with CpG in endosome/lysosome compartments. Cells lacking Ly49Q showed a disturbed redistribution of TLR9 and CpG. In particular, CpG-induced tubular endolysosomal extension was impaired in the absence of Ly49Q. Consistent with these findings, cells lacking Ly49Q showed impaired cytokine production in response to CpG-oligodeoxynucleotide. Our data highlight a novel mechanism by which TLR9 signaling is controlled through the spatiotemporal regulation of membrane trafficking by the immunoreceptor tyrosine-based inhibitory motif–bearing receptor Ly49Q. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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