Role of prognostic biomarker decoy receptor 3 and immunomodulation in kidney diseases.

Abstract

Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member 6b (TNFRSF6B), was recently identified as a novel biomarker for predicting progression of kidney diseases with potential immune modulation. The purpose of this review is to discuss the current evidence related to DcR3 in kidney diseases and to compare the differences between human and animal studies both in vivo and in vitro. High serum DcR3 predicts the occurrence of peritonitis in patients receiving chronic peritoneal dialysis and is positively correlated with inflammatory markers such as interleukin-6, high-sensitivity C-reactive protein, and adhesion molecules in patients on maintenance hemodialysis (HD). Higher serum DcR3 levels not only independently predict cardiovascular and all-cause mortality in HD patients but also identify older adults on HD at risk of protein-energy wasting in combination with a low geriatric nutritional risk index. Recently, renal tubular epithelial cells (RTECs) expressing DcR3 have also been used to predict progression of chronic kidney disease. Expression of DcR3 was correlated with a 2-fold increase in serum creatinine or failure of kidney allograft. DcR3 could protect renal myofibroblasts against Fas-induced apoptosis and subsequently lead to renal fibrosis. Locally expressed DcR3 in the RTECs may suppress the FasL-Fas-mediated apoptosis of T cells, resulting in an accumulation of allo-reactive T cells. In addition to traditional biological functions, recombinant DcR3.Fc and cytomegalovirus promoter-driven human DcR3 plasmid are able to modulate the activation and differentiation of dendritic cells and macrophages via "non-decoy" action. Both progressive IgA nephropathy and autoimmune crescentic glomerulonephritis in mice can be suppressed after hydrodynamics-based gene delivery of DcR3 plasmid. DcR3-mediated effects in vitro could be surveyed via over-expressing DcR3 or addition of recombinant DcR3.Fc, and CD68-driven DcR3 transgenic mice are suitable for investigating systemic effect in vivo. Inhibition of DcR3 expression in human may be a promising approach for pathomechanism.