A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis

TR6 (decoy receptor 3 (DcR3)) is a new member of the tumor necrosis factor receptor (TNFR) family. TR6 mRNA is expressed in lung tissues and colon ade nocarcinoma, SW480. In addition, the expression of TR6 mRNA was shown in th e endothelial cell line and induced by phorbol 12-myristate 13-acetate/iono mycin in Jurkat T leukemia cells. The open reading frame of TR6 encodes 300 amino acids with a 29-residue signal sequence but no transmembrane region. Using histidine-tagged recombinant TR6, we screened soluble forms of TNF-l igand proteins with immunoprecipitation. Here, we demonstrate that TR6 spec ifically binds two cellular ligands, LIGHT (herpes virus entry mediator (HV EM)-L) and Fas ligand (FasL/CD95L). These bindings were confirmed with HEK 293 EBNA cells transfected with LIGHT cDNA by flow cytometry. TR6 inhibited LIGHT-induced cytotoxicity in HT29 cells. It has been shown that LIGHT tri ggers apoptosis of various tumor cells including HT29 cells that express bo th lymphotoxin beta receptor (LT beta R) and HVEM/TR2 receptors. Our data s uggest that TR6 inhibits the interactions of LIGHT with HVEM/TR2 and LT bet a R, thereby suppressing LIGHT-mediated HT29 cell death. Thus, TR6 may play a regulatory role for suppressing in FasL- and LIGHT-mediated cell death.