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      Decoy receptor 3: an endogenous immunomodulator in cancer growth and inflammatory reactions

      review-article
      1 , 2 , 3 , 4 , 5 , , 6 ,
      Journal of Biomedical Science
      BioMed Central
      Decoy receptor 3 (DcR3), M2 macrophages, Biomarker, TNFR6B

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          Abstract

          Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor (TNFR) superfamily member 6b (TNFRSF6B), is a soluble decoy receptor which can neutralize the biological functions of three members of tumor necrosis factor superfamily (TNFSF): Fas ligand (FasL), LIGHT, and TL1A. In addition to ‘decoy’ function, recombinant DcR3.Fc is able to modulate the activation and differentiation of dendritic cells (DCs) and macrophages via ‘non-decoy’ action. DcR3-treated DCs skew T cell differentiation into Th2 phenotype, while DcR3-treated macrophages behave M2 phenotype. DcR3 is upregulated in various cancer cells and several inflammatory tissues, and is regarded as a potential biomarker to predict inflammatory disease progression and cancer metastasis. However, whether DcR3 is a pathogenic factor or a suppressor to attenuate inflammatory reactions, has not been discussed comprehensively yet. Because mouse genome does not have DcR3, it is not feasible to investigate its physiological functions by gene-knockout approach. However, DcR3-mediated effects in vitro are determined via overexpressing DcR3 or addition of recombinant DcR3.Fc fusion protein. Moreover, CD68-driven DcR3 transgenic mice are used to investigate DcR3-mediated systemic effects in vivo. Upregulation of DcR3 during inflammatory reactions exerts negative-feedback to suppress inflammation, while tumor cells hijack DcR3 to prevent apoptosis and promote tumor growth and invasion. Thus, ‘switch-on’ of DcR3 expression may be feasible for the treatment of inflammatory diseases and enhance tissue repairing, while ‘switch-off’ of DcR3 expression can enhance tumor apoptosis and suppress tumor growth in vivo.

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          Most cited references102

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          TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.

          DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect.
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            Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer.

            Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apol/CD95. One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.
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              Surgical Approaches to Create Murine Models of Human Wound Healing

              Wound repair is a complex biologic process which becomes abnormal in numerous disease states. Although in vitro models have been important in identifying critical repair pathways in specific cell populations, in vivo models are necessary to obtain a more comprehensive and pertinent understanding of human wound healing. The laboratory mouse has long been the most common animal research tool and numerous transgenic strains and models have been developed to help researchers study the molecular pathways involved in wound repair and regeneration. This paper aims to highlight common surgical mouse models of cutaneous disease and to provide investigators with a better understanding of the benefits and limitations of these models for translational applications.
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                Author and article information

                Contributors
                886-2-27871245 , slhsieh@gate.sinica.edu.tw
                886-2-23123456 , wwllaura1119@ntu.edu.tw
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                19 June 2017
                19 June 2017
                2017
                : 24
                : 39
                Affiliations
                [1 ]ISNI 0000 0001 2287 1366, GRID grid.28665.3f, , Genomics Research Center, Academia Sinica, ; 128 Academia Road, Section 2, Nankang, Taipei, 115 Taiwan
                [2 ]ISNI 0000 0001 0425 5914, GRID grid.260770.4, , Institute of Clinical Medicine & Immunology Research Center, National Yang-Ming University, ; Taipei, Taiwan
                [3 ]ISNI 0000 0004 0604 5314, GRID grid.278247.c, , Department of Medical Research and Education, Taipei Veterans General Hospital, ; Taipei, Taiwan
                [4 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, , Institute of Immunology, College of Medicine, National Taiwan University Taipei, ; Taipei, Taiwan
                [5 ]ISNI 0000 0000 9337 0481, GRID grid.412896.0, , Institute for Cancer Biology and Drug Discovery, Taipei Medical University, ; Taipei, Taiwan
                [6 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Department of Pharmacology, College of Medicine, , National Taiwan University, ; No. 1 Section 1, Jen Ai Road, Taipei, 10001 Taiwan
                Article
                347
                10.1186/s12929-017-0347-7
                5477258
                28629361
                35fce4fc-2600-4b58-bd11-c9dc0d9ac439
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 March 2017
                : 13 June 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: 103-2320-B001-010-MY3
                Award ID: 103-2321-B-002-105
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Molecular medicine
                decoy receptor 3 (dcr3),m2 macrophages,biomarker,tnfr6b
                Molecular medicine
                decoy receptor 3 (dcr3), m2 macrophages, biomarker, tnfr6b

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