Decoy receptor 3: An endogenous immunomodulator in cancer growth and inflammatory reactions
Journal
Journal of Biomedical Science
Journal Volume
24
Journal Issue
1
Pages
39
Date Issued
2017
Author(s)
Hsieh S.-L.
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. ? 2017 The Author(s).
Subjects
Biomarker; Decoy receptor 3 (DcR3); M2 macrophages; TNFR6B
SDGs
Other Subjects
biological marker; death receptor 3; decoy receptor 3; recombinant decoy receptor 3 Fc fusion protein; recombinant protein; tumor marker; unclassified drug; decoy receptor 3; immunologic factor; TNFRSF6B protein, human; apoptosis; B lymphocyte; bone marrow cell; cancer growth; cancer immunotherapy; cancer inhibition; cell differentiation; dendritic cell; disease course; disease severity; drug effect; gene expression; gene overexpression; gene silencing; gene therapy; homeostasis; human; immunomodulation; in vitro gene transfer; in vivo gene transfer; inflammation; inflammatory disease; macrophage; malignant neoplasm; metastasis; mutation; nonhuman; priority journal; protein blood level; protein expression; protein function; receptor upregulation; Review; rheumatoid arthritis; synoviocyte; tissue repair; tumor cell; upregulation; animal; apoptosis; gene expression regulation; genetics; inflammation; metabolism; mouse; neoplasm; transgenic animal; Animals; Animals, Genetically Modified; Apoptosis; Gene Expression Regulation; Humans; Immunologic Factors; Inflammation; Mice; Neoplasms; Receptors, Tumor Necrosis Factor, Member 6b
Type
review