TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator

  • Immunity. 2002 Mar;16(3):479-92. doi: 10.1016/s1074-7613(02)00283-2.
Thi Sau Migone  1 ,  Jun Zhang ,  Xia Luo ,  Li Zhuang ,  Cecil Chen ,  Bugen Hu ,  June S Hong ,  James W Perry ,  Su Fang Chen ,  Joe X H Zhou ,  Yun Hee Cho ,  Stephen Ullrich ,  Palanisamy Kanakaraj ,  Jeffrey Carrell ,  Ernest Boyd ,  Henrik S Olsen ,  Gang Hu ,  Laurie Pukac ,  Ding Liu ,  Jian Ni ,  Sunghee Kim ,  Reiner Gentz ,  Ping Feng ,  Paul A Moore ,  Steve M Ruben ,  Ping Wei
Affiliations
  • 1. Human Genome Sciences, Inc., Rockville, MD 20850, USA.
PMID: 11911831 DOI: 10.1016/s1074-7613(02)00283-2
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.

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