DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts.

Masayasu Takahashi, Yasushi Miura, Shinya Hayashi, Koji Tateishi, Koji Fukuda, Masahiro Kurosaka

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.

International journal of molecular medicine 2011 Sep

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Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TL1A. We previously reported that TNFα-induced DcR3 overexpression in rheumatoid synovial fibroblasts (RA-FLS) protects the cells from Fas-induced apoptosis and that DcR3 induces VLA-4 expression in THP-1 macrophages to inhibit cycloheximide-induced apoptosis. Meanwhile, recent studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages to osteoclasts. Therefore, in the present study, we analyzed the direct effects of DcR3 as a ligand in RA-FLS. The experiments showed that DcR3 binds to TL1A expressed in RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. DcR3-TL1A signalling may be involved in the pathogenesis of rheumatoid arthritis (RA).

Citation

Masayasu Takahashi, Yasushi Miura, Shinya Hayashi, Koji Tateishi, Koji Fukuda, Masahiro Kurosaka. DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts. International journal of molecular medicine. 2011 Sep;28(3):423-7