Cytokine dysregulation induced by apoptotic cells is a shared characteristic of murine lupus.
Of the multiple murine models of autoimmunity, the three most closely resembling human systemic lupus erythematosus (SLE) are the MRL/lpr, New Zealand Black/White F(1), and male BXSB. Although these strains share many disease characteristics, no common cellular defect has previously been found in prediseased mice from all these strains. We show in this study that macrophages from prediseased mice of all three SLE-prone strains, as well as macrophages from mice whose genomes contribute to the development of SLE (MRL/+, New Zealand White, New Zealand Black, female BXSB, and LG/J), have an identical and profound defect in cytokine expression that is triggered by apoptotic cells. Strikingly, none of 13 nonautoimmune strains tested exhibited this defect. Given that apoptotic Ags have been increasingly recognized as the target of autoantibodies, a defect in cytokine expression that is triggered by apoptotic cells has broad potential to upset the balance between tolerance and immunity.
Koh
J S
JS
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Wang
Z
Z
Levine
J S
JS
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000096:biosynthesis* / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D008055:Lipids / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines; D007375:Interleukin-1; D008055:Lipids