Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase.
Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.
Cohen
Philip L
PL
Department of Medicine, Division of Rheumatology, University of Pennsylvania, and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. philipco@mail.med.upenn.edu
Caricchio
Roberto
R
Abraham
Valsamma
V
Camenisch
Todd D
TD
Jennette
J Charles
JC
Roubey
Robert A S
RA
Earp
H Shelton
HS
Matsushima
Glenn
G
Reap
Elizabeth A
EA
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology; D002843:Chromatin / Q000276:immunology; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes; D005920:Glomerular Mesangium / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010587:Phagocytosis / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011507:Proteinuria / Q000150:complications / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D012217:Rheumatoid Factor / Q000097:blood; D012235:Rhodamines; D000076202:c-Mer Tyrosine Kinase
C114557:5-carboxytetramethylrhodamine succinimidyl ester; D001323:Autoantibodies; D002308:Cardiolipins; D002843:Chromatin; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D011518:Proto-Oncogene Proteins; D012235:Rhodamines; D004247:DNA; D012217:Rheumatoid Factor; C490767:Mertk protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase