Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus

Abstract

SummaryDecoy receptor 3 (DcR3/TR6) is a decoy receptor for the Fas ligand (FasL) and can inhibit FasL-induced apoptosis. It has been reported recently that DcR3 can induce T cell activation via co-stimulation of T cells, suggesting that DcR3 may be involved in the pathophysiology of autoimmune diseases. This study aims to analyse the serum DcR3 in patients with systemic lupus erythematosus (SLE) and to investigate the role of DcR3 in the pathogenesis of SLE. Significantly elevated serum DcR3 was observed in SLE patients, and the mean serum DcR3 level was significantly higher for those with active disease [SLE disease activity index (SLEDAI) Ն 10] compared with that in patients with inactive disease (SLEDAI < 10). In addition to reducing activationinduced cell death in activated T cells via neutralization of the FasL, soluble DcR3-Fc enhanced T cell proliferation and increased interleukin-2 and interferon-g production via co-stimulation of T cells. Moreover, enhanced T cell reactivity to DcR3-induced co-stimulation was demonstrated in lymphocytes from patients with SLE, suggesting the elevated serum DcR3 may associate with enhanced T cell activation in vivo. These findings are the first to demonstrate that serum DcR3 concentrations are increased in SLE patients, and this may imply a possible role of DcR3 in the pathogenesis of SLE via enhanced T cell hyperreactivity and reduced apoptosis in activated T cells.

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis

“…Studies in other rheumatic diseases showed the increase of DcR3 in the serum of systemic lupus erythematosus (SLE) and indicated high disease activity [9]. Consistently, elevated levels of DcR3 were also found in systemic sclerosis (SSc), psoriatic skin lesions and inflammatory bowel diseases [10][11][12].…”

Lipid Raft Assembly and Lck Recruitment in TRAIL Costimulation Mediates NF-κB Activation and T Cell Proliferation

“…T cells were separated by Rosette separation (Stem Cell Technologies, Vancouver, BC, Canada) as previously described (12,21). Briefly, non-T cells were selected by a tetrameric Ab mixture against CD14, CD16, CD19, CD56, and glyA and bound to erythrocytes.…”

Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-κB-Dependent Pathway

“…DcR3 induces dendritic cell apoptosis (6), modulates the differentiation of dendritic cells and macrophages and impairs macrophage function (7)(8)(9), regulates T cell/B cell activation, prevents T cell/ macrophage infiltration in the kidney (10), and inhibits T cell chemotaxis (11). Moreover, several reports link DcR3 with immune disease, e.g., DcR3 increases T cell activation in systemic lupus erythematosus (12), osteoclast formation (9,13), and adhesion molecule expression on endothelial cells (14), and overexpression of DcR3 is seen in EBV-or human T-lymphotropic virus type 1-associated lymphomas (15). In addition, an association between DcR3 expression and tumor progression is well documented (16,17).…”