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Blood, 1 July 2007, Vol. 110, No. 1, pp. 242-250. Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2006-11-059980. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-11-059980v1 110/1/242    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 Citing Articles via Google Scholar Google Scholar Articles by Izawa, T. Articles by Hayashi, Y. Search for Related Content PubMed PubMed Citation Articles by Izawa, T. Articles by Hayashi, Y. Related Collections Immunobiology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance Takashi Izawa1,2, Naozumi Ishimaru1, Keiji Moriyama2, Masayuki Kohashi1, Rieko Arakaki1, and Yoshio Hayashi1 1 Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramotocho, Tokushima, Japan; 2 Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramotocho, Tokushima, Japan Although receptor activator of nuclear factor (NF)–B ligand (RANKL) signaling has been shown to prolong the survival of mature dendritic cells (DCs), the association of RANKL pathway with Fas-mediated apoptosis is obscure. Here, we found that bone marrow–derived DCs (BMDCs) from the Fas-deficient strain MRL/lpr mice, could survive much longer than normal DCs. The expressions of Bcl-x and Bcl-2 and the nuclear transport of NF-B of RANKL-stimulated BMDCs from MRL/lpr mice were significantly up-regulated. By contrast, Fas expression of BMDCs from normal C57BL/6 and MRL+/+ mice was increased by RANKL stimulation, and an enhanced DC apoptosis was found when stimulated with both RANKL and anti-Fas mAb, which was associated with activation of caspase-3 and caspase-9. Furthermore, the expression of FLIPL, an inhibitory molecule against Fas-mediated apoptosis, in normal DCs was significantly decreased by RANKL and anti-Fas mAb. Indeed, the adoptive transfer of RANKL-stimulated DCs resulted in rapid acceleration of autoimmunity in MRL/lpr recipients. These findings indicate that the crosstalk between RANKL and Fas signaling in DCs might control immune tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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