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Decoy Receptor 3 Ameliorates an Autoimmune Crescentic Glomerulonephritis Model in Mice

Shuk-Man Ka^*, Huey-Kang Sytwu^,, Deh-Ming Chang, Shie-Liang Hsieh^||, Pei-Yi Tsai and Ann Chen^*

^* Department of Pathology, Division of Rheumatology/Immunology & Allergy, Department of Medicine, Tri-Service General Hospital, Graduate Institute of Medical Sciences, Department of Microbiology and Immunology, National Defense Medical Center, and ^|| Institute and Department of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China

Correspondence: Dr. Ann Chen, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC, Phone: +886-2-8792-7008; Fax: +886-2-8792-7009; E-mail: doc31717{at}ndmctsgh.edu.tw

Received for publication November 15, 2006. Accepted for publication May 24, 2007.

Autoimmune crescentic glomerulonephritis (ACGN) is a variant of crescentic glomerulonephritis. The outcome of treatment of crescentic glomerulonephritis is poor. Binding of decoy receptor 3 (DCR3) to its ligand is capable of downregulating the alloresponsiveness of T cells. DCR3 has also been shown to benefit an experimental autoimmune model of diabetes. This study tested the hypothesis that a potential immune regulator, DCR3, could prevent the evolution of ACGN. With the use of an established ACGN model in mice, mice were treated with 100 µg/10 g body wt human DCR3 by hydrodynamics-based gene delivery at 14-d intervals. The results showed that the gene therapy resulted in (1) suppression of T and B cell activation and T cell proliferation; (2) a reduction in serum levels of proinflammatory cytokines; (3) improvement of proteinuria and renal dysfunction; (4) prevention of glomerular crescent formation, renal interstitial inflammation, and glomerulosclerosis; (5) a reduction in serum levels of autoantibodies and glomerular immune deposits; (6) inhibition of apoptosis in the spleen and kidney; (7) prevention of T cell and macrophage infiltration of the kidney; and (8) suppression of fibrosis-related gene expression in the kidney compared with empty vector–treated (disease control) ACGN mice. On the basis of these findings, it is proposed that human DCR3 exerts its preventive and protective effects on ACGN through modulation of T cell activation/proliferation, B cell activation, protection against apoptosis, and suppression of mononuclear leukocyte infiltration in the kidney.

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				P.-H. Chen and C.-R. Yang Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-{kappa}B-Dependent Pathway J. Immunol., December 15, 2008; 181(12): 8441 - 8449. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673