Abstract
Autoimmune glomerulonephritis is a common manifestation of systemic lupus erythematosus (SLE). In this study, we show that mice lacking macrophage expression of the heterodimeric nuclear receptors PPARγ or RXRα develop glomerulonephritis and autoantibodies to nuclear Ags, resembling the nephritis seen in SLE. These mice show deficiencies in phagocytosis and clearance of apoptotic cells, and they are unable to acquire an anti-inflammatory phenotype upon feeding of apoptotic cells, which is critical for the maintenance of self-tolerance. These results demonstrate that stimulation of PPARγ and RXRα in macrophages facilitates apoptotic cell engulfment, and they provide a potential strategy to avoid autoimmunity against dying cells and to attenuate SLE.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Antinuclear / biosynthesis
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Antibodies, Antinuclear / metabolism
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Antibodies, Antinuclear / physiology
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Apoptosis / genetics
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Apoptosis / immunology*
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Female
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Lupus Nephritis / genetics
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Lupus Nephritis / immunology*
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Lupus Nephritis / pathology*
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Macrophages / immunology*
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Macrophages / metabolism
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Macrophages / pathology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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PPAR gamma / deficiency*
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PPAR gamma / genetics
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PPAR gamma / physiology
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Phagocytosis / genetics
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Phagocytosis / immunology*
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Retinoid X Receptor alpha / deficiency*
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Retinoid X Receptor alpha / genetics
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Retinoid X Receptor alpha / physiology
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Self Tolerance / genetics
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Self Tolerance / immunology
Substances
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Antibodies, Antinuclear
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PPAR gamma
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Retinoid X Receptor alpha