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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 (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 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 Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 28, 2007 Accepted November 12, 2007 Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3) Ren-In You, Yung-Chi Chang, Po-Min Chen, Wei-Shu Wang, Tsui-Ling Hsu, Chih-Ya Yang, Chun-Ting Lee, and Shie-Liang Hsieh* Institute and Department of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan Division Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan National Yang-Ming University School of Medicine, Taipei, Taiwan Genomics Research Center, Academia Sinica, Taipei, Taiwan Immunology Research Center, Taipei Veterans General Hospital, Taipei, Taiwan * Corresponding author; email: slhsieh{at}ym.edu.tw. Decoy receptor 3 (DcR3) is a soluble decoy receptor belonging to the TNFR superfamily, and its expression is not only upregulated in cancer cells derived from various cell lineages, but also correlates with overall survival of cancer patients. It has been shown that DcR3 sensitize cells of hematopoietic origin to TRAIL-induced apoptosis, therefore we asked whether DcR3 downregulated host immunity by inducing immune cells apoptosis. We demonstrate that DcR3 induces dendritic cell (DC) apoptosis by activating PKC- and JNK subsequently to upregulate 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 DC, 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: C.-Y. Chen, K.-Y. Yang, M.-Y. Chen, H.-Y. Chen, M.-T. Lin, Y.-C. Lee, R.-P. Perng, S.-L. Hsieh, P.-C. Yang, and T.-Y. Chou Decoy Receptor 3 Levels in Peripheral Blood Predict Outcomes of Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., October 15, 2009; 180(8): 751 - 760. [Abstract] [Full Text] [PDF] C.-H. Ho, C.-L. Chen, W.-Y. Li, and C.-J. Chen Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion Carcinogenesis, August 1, 2009; 30(8): 1443 - 1451. [Abstract] [Full Text] [PDF] H.-F. Chen, J.-S. Chen, C.-T. Shun, Y.-F. Tsai, and H.-N. Ho Decoy receptor 3 expression during the menstrual cycle and pregnancy, and regulation by sex steroids in endometrial cells in vitro Hum. Reprod., June 1, 2009; 24(6): 1350 - 1358. [Abstract] [Full Text] [PDF] M. Razmara, B. Hilliard, A. K. Ziarani, R. Murali, S. Yellayi, M. Ghazanfar, Y. H. Chen, and M. L. Tykocinski Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis Am. J. Pathol., February 1, 2009; 174(2): 460 - 474. [Abstract] [Full Text] [PDF] P.-H. Chen and C.-R. Yang Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-{kappa}B-Dependent Pathway J. Immunol., December 15, 2008; 181(12): 8441 - 8449. [Abstract] [Full Text] [PDF] E. Roosnek, P. Schneider, and B. Huard Heparan sulfate proteoglycans, Fc receptors, and DC suppression Blood, August 1, 2008; 112(3): 915 - 916. [Full Text] [PDF] S.-L. Hsieh Response: Decoy receptor 3 (DcR3), a pleiotropic immunomodulator Blood, August 1, 2008; 112(3): 916 - 917. [Full Text] [PDF] 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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