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 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.
Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
Tamás
T
Roszer
María P
MP
Menéndez-Gutiérrez
Martina I
MI
Lefterova
Daniel
D
Alameda
Vanessa
V
Núñez
Mitchell A
MA
Lazar
Thierry
T
Fischer
Mercedes
M
Ricote
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D005260:Female; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D047490:Retinoid X Receptor alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha