Autoimmune Kidney Disease and Impaired Engulfment of Apoptotic Cells in Mice with Macrophage Peroxisome Proliferator-Activated Receptor gamma or Retinoid X Receptor alpha Deficiency

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.