Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 1, Pages 621-631Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1002230
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Funding
- Spanish Ministry of Science and Innovation [SAF2009-07466]
- Fundacion Genoma Espana, and Marato
- Fundacion Genoma Espana
- Spanish Ministry of Health [FIS PI052270]
- People Marie Curie Intra-European Fellowships Program
- Ramon y Cajal Program
- Spanish Ministry of Science and Innovation
- Pro-CNIC Foundation
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK049780] Funding Source: NIH RePORTER
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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 PPAR gamma or RXR alpha 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 PPAR gamma and RXR alpha in macrophages facilitates apoptotic cell engulfment, and they provide a potential strategy to avoid autoimmunity against dying cells and to attenuate SLE. The Journal of Immunology, 2011, 186: 621-631.
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