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Decoy receptor 3 ameliorates an autoimmune crescentic glomerulonephritis model in mice.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2007 Sep; Vol. 18 (9), pp. 2473-85. Date of Electronic Publication: 2007 Aug 08. - Publication Year :
- 2007
-
Abstract
- 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 microg/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.
- Subjects :
- Animals
Apoptosis drug effects
Autoimmune Diseases blood
Autoimmune Diseases prevention & control
B-Lymphocytes
Cytokines blood
Female
Fibrosis
Gene Expression drug effects
Gene Transfer Techniques
Glomerulonephritis blood
Glomerulonephritis prevention & control
Humans
Inflammation Mediators blood
Kidney drug effects
Kidney pathology
Kidney physiopathology
Lymphocyte Activation drug effects
Macrophages pathology
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Receptors, Tumor Necrosis Factor, Member 6b blood
Receptors, Tumor Necrosis Factor, Member 6b genetics
Spleen physiopathology
T-Lymphocytes pathology
Autoimmune Diseases pathology
Autoimmune Diseases physiopathology
Glomerulonephritis pathology
Glomerulonephritis physiopathology
Receptors, Tumor Necrosis Factor, Member 6b pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1046-6673
- Volume :
- 18
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 17687076
- Full Text :
- https://doi.org/10.1681/ASN.2006111242