RGD Reference Report - Renal cell-expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis. - Rat Genome Database

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Renal cell-expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis.

Authors: Vielhauer, V  Stavrakis, G  Mayadas, TN 
Citation: Vielhauer V, etal., J Clin Invest. 2005 May;115(5):1199-209. Epub 2005 Apr 1.
RGD ID: 7245530
Pubmed: PMID:15841213   (View Abstract at PubMed)
PMCID: PMC1070636   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI23348   (Journal Full-text)

TNF is essential for the development of glomerulonephritis, an immune-mediated disorder that is a major cause of renal failure worldwide. However, TNF has proinflammatory and immunosuppressive properties that may segregate at the level of the 2 TNF receptors (TNFRs), TNFR1 and TNFR2. TNFR1-deficient mice subjected to immune complex-mediated glomerulonephritis developed less proteinuria and glomerular injury, and fewer renal leukocyte infiltrates at early time points after disease induction, and this was associated with a reduced systemic immune response to nephrotoxic rabbit IgG. However, proteinuria and renal pathology were similar to those in wild-type controls at later time points, when lack of TNFR1 resulted in excessive renal T cell accumulation and an associated reduction in apoptosis of these cells. In sharp contrast, TNFR2-deficient mice were completely protected from glomerulonephritis at all time points, despite an intact systemic immune response. TNFR2 was induced on glomerular endothelial cells of nephritic kidneys, and TNFR2 expression on intrinsic cells, but not leukocytes, was essential for glomerulonephritis and glomerular complement deposition. Thus, TNFR1 promotes systemic immune responses and renal T cell death, while intrinsic cell TNFR2 plays a critical role in complement-dependent tissue injury. Therefore, therapeutic blockade specifically of TNFR2 may be a promising strategy in the treatment of immune-mediated glomerulonephritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glomerulonephritis  ISOTnfrsf1b (Mus musculus)7245530; 7245530 RGD 
glomerulonephritis  IMP 7245530 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfrsf1b  (TNF receptor superfamily member 1B)

Genes (Mus musculus)
Tnfrsf1b  (tumor necrosis factor receptor superfamily, member 1b)

Genes (Homo sapiens)
TNFRSF1B  (TNF receptor superfamily member 1B)


Additional Information