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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1480-1488. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-09-114850. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-114850v1 111/3/1480    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 You, R.-I. Articles by Hsieh, S.-L. Search for Related Content PubMed PubMed Citation Articles by You, R.-I. Articles by Hsieh, S.-L. Related Collections Immunobiology Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3) Ren-In You1, Yung-Chi Chang1, Po-Min Chen2,3, Wei-Shu Wang2,3, Tsui-Ling Hsu4, Chih-Ya Yang1, Chun-Ting Lee1, and Shie-Liang Hsieh1,4,5 1 Institute and Department of Microbiology and Immunology, National Yang-Ming University; Taipei; 2 Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei; 3 National Yang-Ming University School of Medicine, Taipei; 4 Genomics Research Center, Academia Sinica, Taipei; and 5 Immunology Research Center, Taipei Veterans General Hospital, Taipei, Taiwan Decoy receptor 3 (DcR3) is a soluble decoy receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, and its expression is not only up-regulated in cancer cells derived from various cell lineages, but also correlates with overall survival of patients with cancer. It has been shown that DcR3 sensitize cells of hematopoietic origin to TNF-related apoptosis-inducing ligand (TRAIL)–induced apoptosis; therefore, we asked whether DcR3 down-regulated host immunity by inducing immune cell apoptosis. We demonstrate that DcR3 induces dendritic cell (DC) apoptosis by activating PKC- and JNK subsequently to up-regulate DR5 to recruit Fas-associated death domain (FADD) to propagate the apoptotic signals. The association of FADD with DR5 results in the formation of death-inducing signaling complex (DISC) to trigger the downstream apoptotic signaling cascade. PKC- is activated via cross-linking of heparan sulfate proteoglycan (HSPG) on DCs, because recombinant protein containing the heparin-binding domain (HBD) of DcR3 and the Fc portion of IgG1, the HBD.Fc fusion protein, is also able to trigger DC apoptosis. This provides the first evidence that cross-linking of HSPG on DCs can activate PKC- to induce DC apoptosis via the formation of DR5 DISC, and elucidates a novel mechanism of DcR3-mediated immunosuppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Heparan sulfate proteoglycans, Fc receptors, and DC suppression Eddy Roosnek, Pascal Schneider, and Bertrand Huard Blood 2008 112: 915-916. [Full Text] [PDF] Response: Decoy receptor 3 (DcR3), a pleiotropic immunomodulator Shie-Liang Hsieh Blood 2008 112: 916-917. [Full Text] [PDF] This article has been cited by other articles: Y.-C. Chang, T.-C. Chen, C.-T. Lee, C.-Y. Yang, H.-W. Wang, C.-C. Wang, and S.-L. Hsieh Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3 Blood, May 15, 2008; 111(10): 5054 - 5063. [Abstract] [Full Text] [PDF]

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