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

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).