title: TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.
abstract: 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.
authors.affiliation: Human Genome Sciences, Inc., Rockville, MD 20850, USA.
authors.forename: Thi Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Zhuang
authors.forename: Cecil
authors.initials: C
authors.lastname: Chen
authors.forename: Bugen
authors.initials: B
authors.lastname: Hu
authors.forename: June S
authors.initials: JS
authors.lastname: Hong
authors.forename: James W
authors.initials: JW
authors.lastname: Perry
authors.forename: Su Fang
authors.initials: SF
authors.lastname: Chen
authors.forename: Joe X H
authors.initials: JX
authors.lastname: Zhou
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Stephen
authors.initials: S
authors.lastname: Ullrich
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Kanakaraj
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Carrell
authors.forename: Ernest
authors.initials: E
authors.lastname: Boyd
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Olsen
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Laurie
authors.initials: L
authors.lastname: Pukac
authors.forename: Ding
authors.initials: D
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.forename: Sunghee
authors.initials: S
authors.lastname: Kim
authors.forename: Reiner
authors.initials: R
authors.lastname: Gentz
authors.forename: Ping
authors.initials: P
authors.lastname: Feng
authors.forename: Paul A
authors.initials: PA
authors.lastname: Moore
authors.forename: Steve M
authors.initials: SM
authors.lastname: Ruben
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C506033:TNFRSF25 protein, human; C505911:TNFRSF6B protein, human; C117026:TNFSF15 protein, human; C506034:Tnfrsf25 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha