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.
Migone
Thi Sau
TS
Human Genome Sciences, Inc., Rockville, MD 20850, USA.
Zhang
Jun
J
Luo
Xia
X
Zhuang
Li
L
Chen
Cecil
C
Hu
Bugen
B
Hong
June S
JS
Perry
James W
JW
Chen
Su Fang
SF
Zhou
Joe X H
JX
Cho
Yun Hee
YH
Ullrich
Stephen
S
Kanakaraj
Palanisamy
P
Carrell
Jeffrey
J
Boyd
Ernest
E
Olsen
Henrik S
HS
Hu
Gang
G
Pukac
Laurie
L
Liu
Ding
D
Ni
Jian
J
Kim
Sunghee
S
Gentz
Reiner
R
Feng
Ping
P
Moore
Paul A
PA
Ruben
Steve M
SM
Wei
Ping
P
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
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