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Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1)
Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1)
- Source :
- The Journal of Immunology. 175:7185-7192
- Publication Year :
- 2005
- Publisher :
- The American Association of Immunologists, 2005.
-
Abstract
- MRL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis. Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-γ. The initial mounting of Th1 responses depends on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1 differentiation was impaired and abnormal Th2 skewing was observed during infection with some intracellular pathogens. Disruption of the WSX-1 gene dramatically changed the pathophysiology of glomerulonephritis developing in MRL/lpr mice. WSX-1−/− MRL/lpr mice developed disease resembling human membranous glomerulonephritis (World Health Organization class V) with a predominance of IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T cells in WSX-1−/− MRL/lpr mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development.
- Subjects :
- Mice, Inbred MRL lpr
medicine.medical_specialty
Glomerular deposits
Immunology
Lupus nephritis
Enzyme-Linked Immunosorbent Assay
Immunoglobulin E
Glomerulonephritis, Membranous
Interferon-gamma
Mice
Th2 Cells
Immune system
Microscopy, Electron, Transmission
immune system diseases
Internal medicine
medicine
Animals
Immunology and Allergy
Receptors, Cytokine
skin and connective tissue diseases
Receptor
biology
Reverse Transcriptase Polymerase Chain Reaction
Intracellular parasite
Glomerulonephritis
Receptors, Interleukin
Th1 Cells
medicine.disease
Immunohistochemistry
Lupus Nephritis
Mice, Mutant Strains
Pathophysiology
Disease Models, Animal
Endocrinology
Immunoglobulin G
biology.protein
Female
Interleukin-4
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....4007e7345efe19122e4c0977f248a984
- Full Text :
- https://doi.org/10.4049/jimmunol.175.11.7185